Indications

Ticagrelor is used to prevent atherothrombotic events in adults with Acute Coronary Syndromes (unstable angina, non-ST elevation Myocardial Infarction [NSTEMI] or ST elevation Myocardial Infarction [STEMI]); this includes patients who are treated medically as well as those who are treated with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).

Pharmacology

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.

Dosage & Administration

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. A maintenance dose of Aspirin above 100 mg decreased the efficacy of Ticagrelor. So, the 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.

Interaction

CYP3A inhibitors: Avoid strong CYP3A inhibitors (eg, ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nife Navir, indinavir, atazanavir, and telithromycin).

CYP3A Inducers: Avoid use with strong CYP3A inducers (eg, rifampicin, dexamethasone, phenytoin, carbamazepine, and phenobarbital).

Aspirin: The use of a maintenance dose of ticagrelor aspirin greater than 100 mg will reduce the effectiveness of ticagrelor.

Simvastatin, Lovastatin: Ticagrelor will increase the serum concentration of simvastatin and lovastatin because these drugs are metabolized by CYP3A4. Avoid doses of simvastatin and lovastatin greater than 40 mg.

Digoxin: Due to inhibition of the P-glycoprotein transporter, monitor digoxin levels at the beginning of treatment with ticagrelor or when any changes occur.

Other concomitant therapies: ticagrelor can be combined with ordinary or low molecular weight heparin, GPIIb / IIIa inhibitors, proton pump inhibitors, β receptor blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. Angiotensin receptor-blocking agents are given in combination.

Contraindications

• Hypersensitivity to Ticagrelor or any of the excipients is a contraindication to taking Ticagrelor.
• Pathological bleeding that is active (peptic ulcer)
• Intracranial hemorrhage history
• Hepatic impairment ranging from moderate to severe
• Ticagrelor in combination with powerful CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir)

Side Effects

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

Pregnancy & Lactation

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

Nursing mothers: Available pharmacodynamic/toxicological data in animals have shown the 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.

Precautions & Warnings

Drugs that limit platelet activity, such as Ticagrelor, increase the risk of bleeding in general.

Ticagrelor’s efficacy was reduced when it was used with aspirin maintenance doses of more than 100 mg. As a result, after the initial loading dose of aspirin (typically 325 mg), take Ticagrelor with a 75-100 mg aspirin maintenance dose.

Patients with significant hepatic impairment have not been investigated with ticagrelor.

Ticagrelor withdrawal: Withdrawing from Ticagrelor increases the risk of myocardial infarction, stent thrombosis, and mortality.

Therapeutic Class

Anti-platelet drugs

Storage Conditions

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

Pharmaceutical Name

Ziska Pharmaceuticals Ltd.