Ticagrelor
Indications
Ticagrelor is used for:
Prevention of thrombotic events, [cardiovascular death (CV), myocardial infarction (MI) and stroke] in patients with acute coronary syndromes (ACS) [unstable angina, non-ST elevation myocardial infarction (NSTEMI) or ST elevation myocardial infarction (STEMI)]; including patients managed with percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG).
Adult Dose
Oral
Acute coronary syndrome
Adult:
Loading dose (following ACS event): 180 mg PO (two 90 mg tablets)
Maintenance dose (for first year following ACS event): 90 mg PO BID
Maintenance dose (after 1 year with history of MI): 60 mg PO BID
Administer with aspirin: Initial aspirin loading dose of 325 mg, then maintenance dose of aspirin of 75-100 mg/day; DO NOT exceed aspirin dose of 100 mg/day.
Hepatic Impairment Moderate to severe: Contraindicated.
Child Dose
Renal Dose
Renal impairment
No dosage adjustment needed
Administration
May be taken with or without food.
Contra Indications
History of Intracranial Hemorrhage: Ticagrelor is not recommended in patients with a history of intracranial hemorrhage (ICH) due to a high risk of recurrent ICH in this population. Active Bleeding: Patients with active pathological bleeding eg, peptic ulcer or intracranial hemorrhage.
Severe Hepatic Impairment: Patients with severe hepatic impairment because of a probable increase in exposure, and it has not been studied in these patients. Severe hepatic impairment increases the risk of bleeding because of reduced synthesis of coagulation proteins.
Hypersensitivity (eg, angioedema) to ticagrelor or to any of the components.
Precautions
Patients w/ increased risk of bleeding (e.g. patients who are likely to undergo surgery or invasive procedures). Patients at risk of bradycardic events; w/ history of asthma or COPD, hyperuricaemia or gouty arthritis. Pregnancy and lactation.
Lactation: Unknown whether distributed in human breast milk; potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account the importance of the drug to the mother
Pregnancy-Lactation
Pregnancy
Available data from case reports on use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes
Animal data
Drug given to pregnant rats and pregnant rabbits during organogenesis caused structural abnormalities in the offspring at maternal doses about 5 to 7 times maximum recommended human dose (MRHD) based on body surface area; when given to rats during late gestation and lactation, pup death and effects on pup growth were seen at ~10 times the MRHD
Lactation
There are no data on presence of drug or metabolites in human milk, effects on breastfed infant, or on milk production
Ticagrelor and its metabolites were present in rat milk at higher concentrations than in maternal plasma; when a drug is present in animal milk, it is likely that the drug will be present in human milk
Breastfeeding is not recommended during therapy
Interactions
Aminocaproic acid or tranexamic acid &/or recombinant clotting factor VIIa may augment haemostatis. NSAIDs, oral anticoagulants &/or fibrinolytics, ketoconazole, clarithromycin, nefazodone, ritonavir, atazanavir, rifampin, dexamethasone, phenytoin, carbamazepine, phenobarb, simvastatin >40 mg, digoxin. Increased Cmax & AUC w/ cyclosporine.
Adverse Effects
Side effects of Ticagrelor :
>10%
Dyspnea (13.8%), Bleeding
1-10%
Headache (6.5%), Cough (4.9%), Dizziness (4.5%), Nausea (4.3%), Atrial fibrillation (4.2%), Hypertension (3.8%), Noncardiac chest pain (3.7%), Diarrhea (3.7%), Back pain (3.6%), Hypotension (3.2%), Fatigue (3.2%), Chest pain (3.1%), Syncope (1.7%)
<1%
Dyspena (0.9%)
Bleeding
Non-CABG related bleeds
Total bleeds (major + minor) (8.7%)
Major bleeds (4.5%)
Fatal/life-threatening (2.1%)
Fatal (0.2%)
Intracranial (fatal/life-threatening) (0.3%)
CABG related bleeds
Total major bleeds (85.8%)
Major bleeds when antiplatelet therapy stopped 5 days before CABG (75%)
Fatal/life-threatening (48.1%)
Fatal (0.9%)
Mechanism of Action
Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and platelet activation. Ticagrelor and its active metabolite are approximately equipotent.