“If this blog helped you out, don’t keep it to yourself—share the link on your socials!” 👍 “Like what you read? Spread the love and share this blog on your social media.” 👍 “Found this useful? Hit share and let your friends know too!” 👍 “If you enjoyed this post, please share the URL with your friends online.” 👍 “Sharing is caring—drop this link on your social media if it helped you.”

Monday, July 28, 2025

Ticagrelor


Generic Name: Ticagrelor
Brand Name: Brilinta (widely used)
Drug Class: P2Y₁₂ receptor antagonist; reversible, direct-acting platelet inhibitor
Dosage Form: 60 mg and 90 mg oral tablets
Route of Administration: Oral
Therapeutic Use: Antiplatelet agent to reduce risk of cardiovascular events, particularly in acute coronary syndrome and post‑stenting

Ticagrelor is a potent, reversible inhibitor of the P2Y₁₂ adenosine diphosphate (ADP) receptor on platelets. It prevents platelet aggregation by blocking ADP binding, thereby inhibiting the final common pathway for platelet activation. Unlike thienopyridines (e.g. clopidogrel), ticagrelor does not require metabolic activation and directly interacts with the receptor. Frequent dosing and reversibility allow predictable onset and offset of effect.

2. Indications and Therapeutic Use

2.1 Acute Coronary Syndrome (ACS)

  • For adults with unstable angina, non‑ST-segment elevation myocardial infarction (NSTEMI), or ST‑elevation myocardial infarction (STEMI)

  • Used in combination with low‑dose aspirin

  • Reduces risk of cardiovascular death, myocardial infarction, and stroke

2.2 Post‑Percutaneous Coronary Intervention (PCI) with Stenting

  • Used for dual antiplatelet therapy after drug-eluting stent or bare-metal stent placement

  • Typically continued for 12 months to prevent stent thrombosis

2.3 Secondary Prevention of Atherothrombotic Events

  • In patients with a prior history of myocardial infarction or established peripheral arterial disease

  • May be used to prevent subsequent thrombotic cardiovascular events

3. Dosage and Administration

3.1 Standard Dosing Regimen

Loading Dose

  • 180 mg (two 90 mg tablets) administered as a single dose, ideally before or at time of PCI

Maintenance Dose (on dual antiplatelet therapy with low-dose aspirin)

  • 90 mg twice daily, starting 12–24 hours after the loading dose, continued for up to 12 months

Alternative Maintenance (for patients at increased bleeding risk after one year)

  • Ticagrelor 60 mg twice daily may be considered for extended therapy past 12 months

3.2 Administration Guidance

  • Take tablets with water, with or without food

  • Do not exceed low-dose aspirin (≤100 mg daily) when on ticagrelor therapy

  • Missed dose: take immediately unless next scheduled dose is within 12 hours; do not double dose

3.3 Duration of Therapy

  • Optimal duration in ACS: usually 12 months

  • Extension beyond one year may be appropriate in high-risk patients (e.g. history of MI or PAD), using lower-dose regimen

4. Mechanism of Action

  • Ticagrelor reversibly binds P2Y₁₂ receptor on platelet surface

  • Blocks ADP-mediated platelet activation and aggregation

  • Rapid and significant platelet inhibition within 30 minutes of loading dose

  • Platelet function begins to recover within 3–5 days after stopping therapy due to reversible binding

  • No need for metabolic activation; efficacy not affected by CYP2C19 poor metabolizer status

5. Pharmacokinetics and Dynamics

5.1 Absorption and Bioavailability

  • Peak plasma concentration achieved 1–3 hours post-dose

  • Oral bioavailability near 36%

  • Twice-daily dosing ensures sustained platelet inhibition

5.2 Distribution

  • Highly protein‑bound (>99%)

  • Widely distributed in systemic circulation

5.3 Metabolism

  • Metabolized by hepatic CYP3A4 and CYP3A5 enzymes

  • Active metabolite present, contributes to overall antiplatelet effect

5.4 Elimination

  • Terminal half-life approximately 7 hours; active metabolite half-life around 8.5 hours

  • Excreted in feces (~57%) and urine (~26%)

5.5 Pharmacodynamic Effect

  • Potent platelet inhibition reduces aggregation by >90%

  • Rapid onset of effect and relatively short offset allow more flexibility

6. Contraindications

  • Active pathological bleeding (e.g. peptic ulcer, intracranial hemorrhage)

  • History of intracranial hemorrhage

  • Severe hepatic impairment

  • Hypersensitivity to ticagrelor or excipients

  • Concurrent strong CYP3A4 inhibitors or inducers

7. Warnings and Precautions

7.1 Bleeding Risk

  • Increased risk of major bleeding events (e.g. gastrointestinal, intracranial)

  • Monitor for signs of bleeding; avoid other anticoagulants unless necessary

7.2 Dyspnea

  • Common side effect; usually mild to moderate; often resolves over time

  • Evaluate for underlying pulmonary or cardiac causes if persistent

7.3 Bradycardia and Heart Block

  • May cause transient ventricular pauses or bradyarrhythmias

  • Monitor in patients with preexisting conduction abnormalities

7.4 Drug Interactions

  • Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) or inducers (e.g., rifampin, phenytoin) can alter drug exposure

  • Co-administration of strong inhibitors: ticagrelor contraindicated

  • Use with moderate inhibitors: dose adjustment or alternative agent may be considered

7.5 Aspirin Dose

  • High-dose aspirin (>100 mg daily) reduces efficacy of ticagrelor; ensure low-dose aspirin only

7.6 Surgery and Procedures

  • Discontinue ticagrelor 5 days before elective surgery with high bleeding risk if possible

  • Continue therapy in urgent PCI cases; coordinate with surgical team

8. Adverse Effects

8.1 Common Reactions

  • Bleeding (most frequent risk)

  • Dyspnea (unexplained shortness of breath)

  • Headache, dizziness

  • Nausea, gastrointestinal discomfort

8.2 Less Common/Ocasionally Serious

  • Major bleeding including fatal events

  • Ventricular pauses, bradycardia, syncope

  • Hypersensitivity reactions, including rash

  • Elevated uric acid levels and risk of gout

8.3 Rare Reactions

  • Thrombocytopenia

  • Elevated liver enzyme levels

  • Atrial fibrillation

9. Drug Interactions

9.1 CYP3A4 Modifiers

  • Avoid strong inhibitors (e.g., itraconazole, ritonavir) – can increase ticagrelor levels and bleeding risk

  • Avoid strong inducers (e.g., carbamazepine, St. John’s wort) – can decrease effect

  • Moderate inhibitors (e.g., diltiazem) require caution; moderate dose reduction or close monitoring

9.2 Other Platelet-Inhibiting Agents

  • Concomitant use with other anticoagulants or antiplatelets increases bleeding risk

  • Use only if benefit outweighs bleeding risk; careful clinical monitoring essential

9.3 Aspirin Interaction

  • High-dose aspirin (>100 mg) significantly reduces ticagrelor’s effectiveness

  • Maintain low-dose aspirin only while on ticagrelor

9.4 Cardiac-Acting Drugs

  • May potentiate bradycardic or hypotensive effect when given with beta-blockers, verapamil, or diltiazem

9.5 Statins and Other Agents

  • Simvastatin or lovastatin doses >40 mg daily should be avoided due to increased statin exposure risk

  • Other cardiovascular medications should be co-administered with consideration of combined effects

10. Use in Specific Populations

10.1 Pregnancy

  • Limited human data; use only if potential benefit justifies risk

  • Animal studies indicate low risk at therapeutic exposure; caution warranted

10.2 Lactation

  • Unknown excretion in human milk; breastfeeding not recommended during ticagrelor therapy

10.3 Pediatric Use

  • Safety and efficacy not established in patients under 18 years

  • No pediatric indications currently approved

10.4 Geriatric Use

  • Older patients exhibit increased bleeding risk

  • Consider lower maintenance dosing beyond one year in selected patients

10.5 Hepatic Impairment

  • Contraindicated in severe hepatic disease

  • Use with caution in moderate impairment; monitor liver function

10.6 Renal Impairment

  • No dose adjustment required in mild to moderate renal insufficiency

  • Use carefully in end-stage renal disease; monitor for bleeding

11. Monitoring Parameters

  • Hemoglobin/hematocrit baseline and periodically for bleeding

  • Signs and symptoms of bleeding (e.g., blood in stool, bruising, hemorrhage)

  • Heart rate and rhythm monitoring in patients with conduction disease or syncope symptoms

  • Liver enzyme assays in moderate hepatic impairment

  • Uric acid levels in patients with gout history

  • Ongoing assessment of dyspnea; consider pulmonary evaluation if persistent

12. Management of Overdose

Possible symptoms:

  • Excessive bleeding

  • Severe bradycardia or syncope

  • Ventricular pauses

  • Gastrointestinal symptoms

Recommended actions:

  • Discontinue ticagrelor immediately

  • Provide supportive therapy (e.g., intravenous fluids, blood products)

  • Use platelet transfusion or recombinant factor VIIa in life‑threatening bleeding

  • Atropine or temporary pacing for symptomatic bradycardia

  • No specific reversal agent; ticagrelor effect diminishes gradually over several days

13. Storage and Handling

  • Store at controlled room temperature (20–25 °C)

  • Protect from moisture and light

  • Keep tablets in original blister packaging until use

  • Do not split or crush tablets

  • Dispense with low-dose aspirin only; warn patients not to take high-dose enteric-coated aspirin

14. Clinical and Therapeutic Considerations

  • Ticagrelor offers rapid, potent, and reversible platelet inhibition without reliance on metabolic activation

  • Preferred over clopidogrel when risk of cardiovascular events outweighs bleeding risk, particularly in non‑CYP2C19 metabolizer populations

  • Dyspnea is more common than with other antiplatelets; often transient and not associated with pulmonary pathology

  • Platelet function recovers more rapidly upon discontinuation compared to irreversible agents

  • Ideal for patients undergoing procedures where antiplatelet discontinuation is planned

  • Extended lower-dose maintenance beyond 12 months may benefit high-risk patients while mitigating long-term bleeding risk

  • Patient education critical: adherence to twice‑daily regimen, avoidance of high‑dose aspirin, bleeding risk awareness, and recognizing dyspnea




on
Labels:

No comments:

Post a Comment

Subscribe to: Post Comments (Atom)