Indications

Ticagrelor, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with acute coronary syndromes (ACS) or a history of myocardial infarction (MI) and a high risk of developing an atherothrombotic event.

Composition

Pharmacology

Ticagrelor is a P2Y 12 receptor antagonist. The P2Y 12 receptor couples with Gα i2 and other G i proteins which inhibit adenylyl cyclase. G i mediated signalling also activates PI3K, Akt, Rap1b, and potassium channels. The downstream effects of these activities mediate hemostasis and lead to platelet aggregation. Antagonism of the P2Y 12 receptor reduces development of occlusive thromboses, which can reduce the risk of myocardial infarction and ischemic stroke.

Dosage & Administration

Patients taking Ticagrelor should also take a daily low maintenance dose of acetylsalicylic acid (ASA) 75-150 mg unless specifically contraindicated. Acute coronary syndromes : 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. Treatment with Ticagrelor twice daily is recommended for 12 months in ACS patients unless discontinuation is clinically indicated. History of myocardial infarction : Ticagrelor 60 mg twice daily is the recommended dose when an extended treatment is required for patients with a history of MI of at least one year and a high risk of an atherothrombotic event. Treatment may be started without interruption as continuation therapy after the initial one-year treatment with ticagrelor or another adenosine diphosphate (ADP) receptor inhibitor therapy in ACS patients with a high risk of an atherothrombotic event. Treatment can also be initiated up to 2 years from the MI, or within one year after stopping previous ADP receptor inhibitor treatment. There are limited data on the efficacy and safety of ticagrelor beyond 3 years of extended treatment. Switch therapy : If a switch is needed, the first dose of ticagrelor should be administered 24 hours following the last dose of the other antiplatelet medication. Missed dose : A patient who misses a dose of ticagrelor should take only one tablet (their next dose) at its scheduled time. Elderly : No dose adjustment is required in the elderly. Renal impairment : No dose adjustment is necessary for patients with renal impairment. No information is available concerning the treatment of patients on renal dialysis and therefore ticagrelor is not recommended in these patients. Hepatic impairment : Ticagrelor has not been studied in patients with severe hepatic impairment and its use in these patients is therefore contraindicated. Only limited information is available in patients with moderate hepatic impairment. Dose adjustment is not recommended, but ticagrelor should be used with caution. No dose adjustment is necessary for patients with mild hepatic impairment. Pediatric population : The safety and efficacy of ticagrelor in hildren below the age of 18 years have not been established. No data are available. Ticagrelor can be administered with or without food. Contra-indications, warnings etc.

Contraindications

Hypersensitivity to the active substance or to any of the excipients, active pathological bleeding, history of intracranial haemorrhage, severe hepatic impairment.

Side Effects

Very Common: Blood disorder bleedings, Hyperuricaemia, Dyspnoea. Common: Gout/Gouty Arthritis, Dizziness, Syncope, Headache, Vertigo, Hypotension, Respiratory system bleedings, Gastrointestinal haemorrhage, Diarrhoea, Nausea, Dyspepsia, Constipation, Subcutaneous or dermal bleeding, Rash, Pruritus, Urinary tract bleeding, Blood creatinine increased, Postprocedural haemorrhage, Traumatic bleedings. Uncommon: Tumour bleedings, Hypersensitivity including angioedema, Confusion, Intracranial haemorrhage, Eye haemorrhage, Ear haemorrhage, Retroperitoneal haemorrhage, Muscular bleedings.

Pregnancy & Lactation

Ticagrelor is not recommended during pregnancy. 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 breast-feeding or to discontinue/abstain from ticagrelor therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Precautions & Warnings

Bleeding risk : The use of ticagrelor in patients at known increased risk for bleeding should be balanced against the benefit in terms of prevention of atherothrombotic events. If clinically indicated, ticagrelor should be used with caution in the following patient groups; Patients with a propensity to bleed (e.g. due to recent trauma, recent surgery, coagulation disorders, active or recent gastrointestinal bleeding). Antifibrinolytic therapy (aminocaproic acid or tranexamic acid) and/or recombinant factor VIIa therapy may increase haemostasis. Ticagrelor may be resumed after the cause of bleeding has been identified and controlled. Surgery : Patients should be advised to inform  physicians and dentists that they are taking ticagrelor before any surgery is scheduled and before any new medicinal product is taken. If a patient is to undergo elective surgery and the antiplatelet effect is not desired, ticagrelor should be discontinued 5 days prior to surgery. Patients with prior ischaemic stroke : ACS patients with prior ischaemic stroke can be treated with ticagrelor for up to 12 months. Patients at risk for bradycardic events: Due to the limited clinical experience, ticagrelor should be used with caution in these patients. Dyspnoea : Patients with asthma/chronic obstructive pulmonary disease (COPD) may have an increased absolute risk of experiencing dyspnoea with ticagrelor. Ticagrelor should be used with caution in patients with a history of asthma and/or COPD. Creatinine elevations: Creatinine levels may increase during treatment with ticagrelor. In patients with ACS, it is recommended that renal function is also checked one month after initiating the treatment with ticagrelor, paying special attention to patients ≥75 years, patients with moderate/severe renal impairment and those receiving concomitant treatment with an angiotensin receptor blocker (ARB). Uric acid increase: Hyperuricaemia may occur during treatment with ticagrelor. Caution is advised in patients with a history of hyperuricaemia or gouty arthritis. Other: Based on a relationship observed in PLATO between maintenance dose of acetylsalicylic acid (ASA) and relative efficacy of ticagrelor compared to clopidogrel, co-administration of ticagrelor and high maintenance dose of acetylsalicylic acid (ASA) (>300 mg) is not recommended. Premature discontinuation : Premature discontinuation with any antiplatelet therapy, including ticagrelor, could result in an increased risk of cardiovascular (CV) death or MI due to the patient’s underlying disease. Therefore, premature discontinuation of treatment should be avoided.

Therapeutic Class

Anti-platelet drugs

Storage Conditions

Store in a cool and dry place, protected from light.