TACLIS TABLETS

Indications

• Prevention of atherothrombotic events in patients with acute coronary syndrome
• Management of patients undergoing percutaneous coronary intervention

Dosage

Adults: Initially, 180 mg orally, followed by 90 mg twice daily, in combination with aspirin.

Mechanism of action

Ticagrelor antagonizes the P2Y12 receptor, which is coupled with Gαi2 and other Gi proteins. This interaction inhibits adenylyl cyclase, reduces cyclic adenosine monophosphate (cAMP) levels, and subsequently decreases platelet activation and aggregation. The drug also inhibits the reuptake of adenosine into erythrocytes, which may contribute to its cardiovascular effects.

Pharmacodynamics

As a P2Y12 receptor antagonist, ticagrelor effectively reduces the formation of occlusive thromboses, thus lowering the incidence of myocardial infarction and ischemic stroke. It has a moderate duration of action and is usually administered twice daily. The drug's therapeutic index is wide, making it well tolerated even at higher doses. Common adverse effects include bleeding, dyspnea, and bradyarrhythmias, necessitating patient counseling.

Pharmacokinetics

Ticagrelor is rapidly absorbed following oral administration, with peak plasma concentrations occurring within 1 to 3 hours. The drug undergoes significant hepatic metabolism, primarily by cytochrome P450 enzymes, and has an elimination half-life of approximately 7 hours. It is excreted mainly through feces and urine, with caution advised in patients with hepatic or renal impairment due to increased bleeding risk.

Contra-indications

• Severe hepatic impairment
• Active bleeding
• History of hypersensitivity to ticagrelor or any component of the formulation

Adverse effects

• Anaemia
• Haemorrhage
• Skin events
• Thrombocytopenia
• Dyspnea
• Bradyarrhythmias
• Angioedema

Interactions

• Cobicistat: Severe (increases exposure)
• Idelalisib: Severe (increases exposure)
• Mitotane: Severe (decreases exposure)
• Rifampicin: Severe (decreases exposure)
• Amiodarone: Moderate (increases exposure)
• Cenobamate: Moderate (decreases exposure)
• Ciclosporin: Moderate (increases exposure)
• Azithromycin: Moderate (increases exposure)
• Ranolazine: Moderate (increases exposure)
• Dabigatran: Moderate (increases exposure)

Precautions

• Use with caution in patients with renal impairment
• Use with caution in patients with moderate hepatic impairment
• Elderly patients at increased risk of bleeding
• Discontinue at least 7 days before elective surgery if antiplatelet effect not desirable

Pregnancy

Manufacturer advises use only if potential benefit outweighs risk.

Breast-feeding

Manufacturer advises to avoid due to lack of information available.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Ticagrelor 90 mg tablets

Mechanism of action

Ticagrelor is a P2Y₁₂ receptor antagonist. The P2Y₁₂ 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 P2Y₁₂ receptor reduces development of occlusive thromboses, which can reduce the risk of myocardial infarction and ischemic stroke. Ticagrelor, a cyclopentyltriazolopyrimidine derivative, is a nonthienopyridine, P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist. In contrast to the thienopyridines (e.g., clopidogrel, prasugrel), ticagrelor binds reversibly to the P2Y12 ADP receptor and does not require hepatic transformation to exert its pharmacologic effect. Ticagrelor exhibits noncompetitive and reversible binding to the P2Y12 platelet ADP receptor, preventing signal transduction of the cyclic adenosine monophosphate (cAMP) pathway. This results in reduced exposure of fibrinogen binding sites to the platelet glycoprotein (GP) IIb/IIIa complex and subsequent inhibition of platelet activation and aggregation. In addition to platelet ADP-receptor blockade, ticagrelor inhibits reuptake of adenosine into erythrocytes, a mechanism that may account for some of the beneficial cardiovascular effects of the drug, while potentially contributing to some of its adverse effects (e.g., dyspnea, ventricular pauses).

Pharmacodynamics

Ticagrelor is a P2Y₁₂ receptor antagonist that inhibits the formation of thromboses to reduce the risk of myocardial infarction and ischemic stroke. It has a moderate duration of action as it is given twice daily, and a wide therapeutic index as high single doses are well tolerated. Patients should be counselled regarding the risk of bleeding, dyspnea, and bradyarrhythmias.