Ticagrelor

Registered South African indications:

• Prevention of thrombotic events

Contraindications

• Hypersensitivity to the active ingredient or to any of its excipients
• Severe hepatic impairment
• Active pathological bleeding
• History of intracranial haemorrhage
• Coadministration with CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir)

Cautions

• Pregnancy
• Breastfeeding
• Moderate hepatic impairment
• Recent trauma
• Recent surgery
• Coagulation disorders
• Active or recent gastrointestinal bleeding
• Antifibrinolytic therapy within 24 hours of ticagrelor dosing
• Patients at risk of bradycardic events
• Asthma/ chronic obstructive pulmonary disease (COPD)
• Hyperuricaemia or gouty arthritis
• Heparin induced thrombocytopenia (HIT)
• Premature discontinuation
• History of cerebrovascular accident
• History of myocardial infarction
• Treatment beyond one year
• Uric acid nephropathy
• Concomitant administration of medicinal products that may increase the risk of bleeding within 24 hours of ticagrelor dosing

Forms avail. in SA and covered in this monograph: tab

Prevention of thrombotic events in patients with acute coronary syndrome
- Medical management
- Percutaneous coronary intervention
- Coronary artery bypass graft

• Oral (tab): Loading dose: 180mg; Maintenance: 90mg, 12hrly; Treatment duration: 12 months

Patients taking ticagrelor should also take a daily low maintenance dose of acetylsalicylic acid (ASA) 75-150 mg, unless specifically contraindicated

If a dose is missed, the patient should take only one tablet at its scheduled time

For patients who are unable to swallow the tablet(s) whole, the tablets can be crushed to a fine powder and mixed in half a glass of water and drunk immediately. The glass should be rinsed with a further half glass of water and the contents drunk. The mixture can also be administered via a nasogastric tube (CH8 or greater). It is important to flush the nasogastric tube through with water after administration of the mixture

Not established for use in children below 18 years

Pregnancy

• Caution; not recommended
• There are no or limited amount of data from the use of ticagrelor in pregnant women
• Women of childbearing potential should use appropriate contraceptive measures to avoid pregnancy during ticagrelor
  therapy

Breastfeeding

• Caution; not recommended 
• 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

Fertility

• Ticagrelor had no effect on male or female fertility in animals

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment 

• Mild: No dose adjustment recommended
• Moderate: Caution; no dose adjustment recommended 
• Severe: Contraindicated

Elderly 

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - no warnings

Central Nervous System Disorders

• Confusion
• Dizziness
• Syncope
• Headache
• Intracranial haemorrhage

Cardiovascular Disorders

• Hypotension

Respiratory Disorders

• Dyspnoea
• Respiratory system bleeding

Gastrointestinal Disorders

• Gastrointestinal haemorrhage
• Diarrhoea
• Nausea
• Dyspepsia
• Constipation
• Retroperitoneal haemorrhage

Genitourinary Disorders

• Urinary tract bleeding
• Reproductive system bleeding

Endocrine and Metabolic Disorders

• Hyperuricaemia
• Gout
• Gouty arthritis
• Increased blood creatinine 

Skin and Subcutaneous Tissue Disorders

• Subcutaneous or dermal bleeding
• Rash
• Pruritus
• Musculoskeletal connective tissue and bone
• Muscular bleeding
• Tumour bleeding

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity including angioedema
• Blood disorder bleedings
• Thrombotic thrombocytopenic purpura

Sensory Disorders

• Eye haemorrhage
• Vertigo
• Ear haemorrhage

Other

• Post procedural haemorrhage
• Traumatic bleeding

• CYP3A4 inhibitors
• Ketoconazole
• Fluconazole
• Clarithromycin
• Erythromycin
• Nefazodone
• Ritonavir
• Atazanavir
• Diltiazem
• Amprenavir
• Aprepitant
• CYP3A4 inducers
• Rifampicin
• Phenytoin
• Carbamazapine
• Phenobarbital
• CYP3A4 substrates
• Simvastatin
• Atorvastatin
• Cispride
• Ergot alkaloids
• Ciclosporin
• Agents that alter haemostasis
• Morphine
• P-glycoprotein substrates
• Digoxin
• Cyclosporin
• Medicine known to induce bradycardia
• Selective serotonin re-uptake inhibitors
• High dose aspirin (>300mg)

• Haemoglobin
• Haematocrit
• Renal function

Specific cases may require

• Uric acid
• ECG monitoring

Ticagrelor is an oral, direct acting, selective and reversibly binding P2Y12 receptor antagonist that prevents adenosine diphosphate ADP- mediated P2Y12 dependent platelet activation and aggregation. Ticagrelor does not prevent ADP binding but when bound to the P2Y12 receptor prevents ADP-induced signal transduction.Since platelets participate in the initiation and/or evolution of thrombotic complications of atherosclerotic disease, inhibition of platelet function has been shown to reduce the risk of CV events such as death, MI or stroke.

Ticagrelor also increases local endogenous adenosine levels by inhibiting the equilibrative nucleoside transporter-1 (ENT-1).

Tablet 90mg

• Brilinta  (AstraZeneca) originator