Usage
- Medical Conditions: Ticagrelor is prescribed to reduce the risk of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of MI. It also reduces the rate of stent thrombosis in patients stented for ACS treatment. It’s also indicated to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events, especially those with type 2 diabetes mellitus, and to reduce the risk of stroke in patients with acute ischemic stroke (NIH stroke scale score ≤5) or high-risk transient ischemic attack (TIA).
- Pharmacological Classification: Antiplatelet agent, P2Y12 receptor antagonist.
- Mechanism of Action: Ticagrelor prevents platelet activation and aggregation by reversibly binding to the P2Y12 receptor, an adenosine diphosphate (ADP) receptor on platelets. This inhibition prevents ADP-induced platelet aggregation, reducing the risk of thrombus formation.
Alternate Names
- International/Regional Variations: None specifically listed.
- Brand Names: Brilinta, Brilique, Ticagrelor Sandoz.
How It Works
- Pharmacodynamics: Ticagrelor reversibly inhibits P2Y12 receptors on platelets, reducing platelet activation and aggregation. This leads to a decreased incidence of thrombotic events.
- Pharmacokinetics:
- Absorption: Rapidly absorbed after oral administration.
- Metabolism: Primarily metabolized by CYP3A4/5 enzymes in the liver to an active metabolite.
- Elimination: Primarily eliminated via hepatic metabolism and biliary excretion. Renal elimination plays a minor role.
- Mode of Action: Ticagrelor directly and reversibly binds to the P2Y12 receptor, preventing ADP-mediated platelet activation and aggregation.
- Receptor Binding/Enzyme Inhibition: Reversible antagonist of the P2Y12 receptor.
- Elimination Pathways: Hepatic metabolism via CYP3A4/5, biliary excretion, and minor renal excretion.
Dosage
Standard Dosage
Adults:
- ACS or History of MI: Loading dose: 180 mg orally once. Maintenance dose: 90 mg orally twice daily for 1 year. Maintenance dose after 1 year: 60 mg orally twice daily.
- CAD (no prior MI or stroke): 60 mg orally twice daily.
- Acute Ischemic Stroke or TIA: Loading dose: 180 mg orally once. Maintenance dose: 90 mg orally twice daily for up to 30 days.
Children: Not established; use is not recommended in individuals under 18 years old.
Special Cases:
- Elderly Patients: No dose adjustment is required, but monitor closely due to increased bleeding risk.
- Patients with Renal Impairment: No dose adjustment necessary.
- Patients with Hepatic Dysfunction: Mild impairment: No dose adjustment. Moderate impairment: Consider risks and benefits, use with caution. Severe impairment: Contraindicated.
- Patients with Comorbid Conditions: Consider potential drug interactions and bleeding risk, especially in patients with bleeding disorders, recent surgery, or concomitant use of anticoagulants or NSAIDs.
Clinical Use Cases
Dosage is not provided in source for:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest)
Dosage Adjustments:
Consider renal/hepatic dysfunction, concomitant medications, and bleeding risk.
Side Effects
Common Side Effects:
Bleeding (e.g., nosebleeds, bruising, prolonged bleeding from cuts), shortness of breath (dyspnea), dizziness, headache, nausea, gastrointestinal upset (diarrhea, indigestion, constipation), rash.
Rare but Serious Side Effects:
Severe bleeding (including intracranial hemorrhage, gastrointestinal bleeding), ventricular pauses and bradycardia (slow heart rate), allergic reactions (angioedema).
Long-Term Effects: Not well defined, but potential for increased bleeding risk with extended use.
Adverse Drug Reactions (ADR): Severe bleeding, allergic reactions (angioedema), bradycardia.
Contraindications
- Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage)
- History of intracranial hemorrhage
- Hypersensitivity to ticagrelor
- Severe hepatic impairment
- Concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, itraconazole).
Drug Interactions
- CYP450 Interactions: CYP3A4 substrate and inhibitor.
- Drug Interactions:
- Strong CYP3A4 inhibitors (increased ticagrelor levels and risk of bleeding)
- Aspirin (recommended at low maintenance dose, high doses decrease ticagrelor effectiveness)
- Anticoagulants (increased bleeding risk)
- NSAIDs (increased bleeding risk)
- Digoxin (monitor digoxin levels)
- Statins (some interactions may occur).
- Other Interactions: Alcohol (moderate consumption generally acceptable, excessive alcohol may increase bleeding risk), smoking (may decrease ticagrelor effectiveness), grapefruit juice.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Not established, not recommended during pregnancy due to potential for fetal harm.
- Breastfeeding: Not recommended, as ticagrelor and its metabolites are excreted in animal milk; potential risk to infants unknown.
Drug Profile Summary
- Mechanism of Action: Reversible P2Y12 receptor antagonist, inhibits platelet aggregation.
- Side Effects: Bleeding, shortness of breath, dizziness, headache, nausea.
- Contraindications: Active bleeding, ICH history, hypersensitivity, severe hepatic impairment, strong CYP3A4 inhibitors.
- Drug Interactions: Strong CYP3A4 inhibitors, aspirin, anticoagulants, NSAIDs.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: See dosage section above.
- Monitoring Parameters: Bleeding signs, hemoglobin/hematocrit, platelet count, heart rate and rhythm.
Popular Combinations
Precautions
- General Precautions: Evaluate for bleeding risk factors, hepatic impairment, and drug interactions before starting therapy. Monitor for bleeding and other adverse events.
- Specific Populations: See special cases in dosage section.
- Lifestyle Considerations: Moderate alcohol consumption, avoid smoking. Driving restrictions not typically necessary unless dizziness or other side effects occur.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Ticagrelor?
A: See dosage section above.
Q2: What are the most common side effects of Ticagrelor?
A: Bleeding (e.g., nosebleeds, easy bruising), shortness of breath (dyspnea), dizziness, headache, and gastrointestinal upset.
Q3: How does Ticagrelor work?
A: It’s a P2Y12 receptor antagonist that reversibly blocks ADP-mediated platelet activation and aggregation, preventing clot formation.
Q4: Can Ticagrelor be used in patients with renal impairment?
A: Yes, no dose adjustment is necessary for renal impairment.
Q5: Is Ticagrelor safe during pregnancy or breastfeeding?
A: No, it’s not recommended during pregnancy or breastfeeding due to potential risks to the fetus or infant.
Q6: What are the contraindications for Ticagrelor?
A: Active bleeding, history of intracranial hemorrhage, hypersensitivity to ticagrelor, severe hepatic impairment, and concomitant use of strong CYP3A4 inhibitors.
Q7: What drugs interact with Ticagrelor?
A: Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin), aspirin (high doses), anticoagulants, NSAIDs, and some statins.
Q8: What should patients be monitored for while taking Ticagrelor?
A: Signs of bleeding, blood counts (hemoglobin, hematocrit, platelets), heart rate and rhythm, and other adverse effects.
Q9: Can patients drink alcohol while taking Ticagrelor?
A: Moderate alcohol consumption is generally acceptable, but excessive alcohol may increase the risk of bleeding.
