TICAGRELOR
Clinical safety rating: safe
Animal studies have demonstrated safety
Ticagrelor is a reversible, direct-acting P2Y12 receptor antagonist that inhibits ADP-induced platelet aggregation.
| Metabolism | Primarily metabolized by CYP3A4 and CYP3A5 to active metabolite; also minor CYP2B6 involvement. Ticagrelor and its active metabolite are substrates of P-glycoprotein (P-gp). |
| Excretion | Approximately 58% of the dose is eliminated via feces and 26% via urine. The parent drug and its active metabolite are primarily excreted in feces via biliary secretion, with renal excretion playing a minor role. |
| Half-life | The terminal elimination half-life of ticagrelor is approximately 7 hours, and for its active metabolite (AR-C124910XX) it is about 9 hours. This supports twice-daily dosing, achieving steady state within 2–3 days. |
| Protein binding | Ticagrelor is 99.6% protein-bound, primarily to albumin and alpha-1-acid glycoprotein. Its active metabolite is 99.7% bound. |
| Volume of Distribution | Volume of distribution is approximately 87 L (or 1.2 L/kg), indicating extensive distribution into tissues beyond plasma volume. |
| Bioavailability | Oral bioavailability is approximately 36% due to first-pass metabolism. No intravenous formulation is available. |
| Onset of Action | Orally: Onset of platelet inhibition occurs within 30 minutes, with maximal effect (IPA) achieved at 2–4 hours after a loading dose. |
| Duration of Action | Duration of antiplatelet effect is approximately 12–24 hours, corresponding to the dosing interval (twice daily). Recovery of platelet function occurs over 2–3 days after discontinuation. |
Loading dose: 180 mg orally once. Maintenance: 90 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. Limited data for GFR <30 mL/min; use with caution. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: contraindicated. Child-Pugh Class C: contraindicated. |
| Pediatric use | Not FDA-approved for pediatric patients; safety and effectiveness not established. |
| Geriatric use | No specific dose adjustment; monitor for bleeding risk due to increased sensitivity and comorbidities. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inhibitors may increase levels and inducers may decrease levels Can cause dyspnea and serious bleeding.
| Breastfeeding | Present in breast milk in animal studies; unknown human M/P ratio. Caution recommended due to potential bleeding risk in the infant. |
| Teratogenic Risk | First trimester: No adequate human data; animal studies show no teratogenicity but delayed fetal development at high doses. Second/third trimester: Risk of maternal hemorrhage causing fetal hypoxia; avoid use in pregnancy unless benefit outweighs risks. |
| Fetal Monitoring |
■ FDA Black Box Warning
Boxed Warning: (A) ticagrelor can cause significant, sometimes fatal bleeding; (B) do not use in patients with active pathological bleeding or history of intracranial hemorrhage; (C) ticagrelor is contraindicated in patients with severe hepatic impairment.
| Common Effects | Bleeding |
| Serious Effects |
["Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage)","History of intracranial hemorrhage","Severe hepatic impairment","Hypersensitivity to ticagrelor or excipients"]
| Precautions | ["Increased risk of bleeding (especially in surgery or trauma; hold 5 days before elective surgery)","Avoid concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin) or inducers (e.g., rifampin, phenytoin)","Use with aspirin: maintenance dose should not exceed 100 mg per day","Bradyarrhythmias (e.g., sick sinus syndrome, high-degree AV block) - monitor","Dyspnea - usually mild and self-limiting, but may require discontinuation","Hepatic impairment - avoid in severe hepatic impairment","Thrombotic thrombocytopenic purpura (TTP) rare","Hypersensitivity reactions"] |
Loading safety data…
| Monitor maternal CBC, signs of bleeding; fetal monitoring for growth and well-being if used in pregnancy. |
| Fertility Effects | No impairment of fertility in animal studies; no human data on reproductive impact. |