BRILINTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BRILINTA (BRILINTA).
Reversible, direct-acting P2Y12 platelet receptor antagonist that inhibits ADP-mediated platelet aggregation.
| Metabolism | Primarily metabolized by CYP3A4; also a substrate of P-glycoprotein. |
| Excretion | Approximately 58% of the total radioactivity is excreted in feces via biliary route, and 26% in urine. Unchanged ticagrelor is minimal in urine (<1%) and feces (<1%). The major metabolite (AR-C124910XX) is also eliminated via feces and urine. |
| Half-life | Ticagrelor: ~7 hours (range 6–8.5 h). AR-C124910XX: ~9 hours. Clinical context: Twice-daily dosing achieves steady state within 2–3 days with minimal accumulation. |
| Protein binding | Ticagrelor: >99.7% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). AR-C124910XX: >99.5% bound. |
| Volume of Distribution | Ticagrelor Vd: 88 L (~1.3 L/kg for a 70 kg individual). Indicates extensive extravascular distribution, including into tissues like the liver and kidneys. |
| Bioavailability | Oral: ~36% (range 30–42%) due to first-pass metabolism. Food increases exposure by 20–40% but does not affect pharmacodynamics; thus, taken with or without food. |
| Onset of Action | Oral: Onset of platelet inhibition occurs within 30 minutes, with near-maximal inhibition (≥80% IPA) achieved by 2 hours after a 180 mg loading dose. |
| Duration of Action | Platelet inhibition persists for 24–48 hours after last dose. Recovery of platelet function occurs over 3–5 days after discontinuation, consistent with reversible binding to P2Y12 receptor. |
| Action Class | P2Y12 inhibitors (ADP receptor) |
| Brand Substitutes | Tikacad 90 Tablet, Brigrel Tablet, Xygrel 90 Tablet, Ticastro 90 Tablet, Ticavic 90 Tablet, Brigrel 60mg Tablet, Tigemac 60mg Tablet, Ticavic 60 Tablet, Torplat 60 Tablet, Ticaplat 60mg Tablet |
Acute coronary syndrome: Loading dose 180 mg orally, then 90 mg orally twice daily. Maintenance therapy for patients with ACS: 90 mg twice daily. For patients with prior MI and high risk for atherothrombotic events: 60 mg orally twice daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Avoid use in severe renal impairment (GFR <30 mL/min) due to lack of data and potential for increased bleeding risk. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). Use with caution in moderate hepatic impairment (Child-Pugh class B) with no dose adjustment recommended; monitor for bleeding. No adjustment needed for mild impairment (Child-Pugh class A). |
| Pediatric use | Safety and efficacy in pediatric patients (<18 years) have not been established; no approved dosing recommendations available. |
| Geriatric use | No specific dose adjustment required based on age alone; monitor renal function and bleeding risk as elderly patients may have increased sensitivity or comorbidities. Consider the 60 mg twice daily regimen for patients with prior MI who are ≥65 years with low body weight (<60 kg) or high bleeding risk, per clinical judgment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BRILINTA (BRILINTA).
| Breastfeeding | Unknown if excreted in human milk; M/P ratio not established. Due to potential for serious adverse reactions in nursing infants (bleeding), breastfeeding is not recommended during therapy. |
| Teratogenic Risk | First trimester: No adequate human studies; animal studies show no teratogenicity at supratherapeutic doses. Second/third trimester: Risk of maternal bleeding, including placental abruption; fetal hemorrhage risk increases near term. Avoid in pregnancy unless essential. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: BLEEDING RISK. BRILINTA increases risk of bleeding, including fatal bleeding. Do not use in patients with active pathological bleeding or history of intracranial hemorrhage.
| Serious Effects |
Active pathological bleeding, history of intracranial hemorrhage, severe hepatic impairment.
| Precautions | Bleeding, dyspnea, coronary artery bypass graft (CABG) surgery bleeding, discontinuation risk, bradyarrhythmias, use in patients with hepatic impairment, and drug interactions. |
| Food/Dietary | Avoid grapefruit products as they may increase the effect of ticagrelor. High-fat meals may reduce the rate of absorption but not the overall exposure; no specific food restrictions are required beyond avoiding grapefruit. |
Loading safety data…
| Monitor maternal complete blood count (CBC) and signs of bleeding (gingival, epistaxis, menorrhagia). Assess fetal heart rate and uterine activity if bleeding suspected. Platelet function monitoring not routine. |
| Fertility Effects | No human data on fertility effects. Animal studies show no impairment of fertility at exposures up to 5 times MRHD. |
| Clinical Pearls | Avoid concurrent use with CYP3A4 strong inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin). Use with caution in patients with a history of intracranial bleeding or active pathological bleeding. Do not use in patients with severe hepatic impairment. Renal impairment does not require dose adjustment. Loading dose of 180 mg should be given as soon as possible after diagnosis of ACS. Maintenance dose is 90 mg twice daily for 12 months, then 60 mg twice daily for patients with prior MI and high risk for atherothrombotic events. Reversal of antiplatelet effect can be achieved with platelet transfusion if needed, but ticagrelor is reversible and its effect diminishes within 3-5 days. |
| Patient Advice | Take BRILINTA exactly as prescribed, with or without food. · Do not skip doses; if you miss a dose, take it as soon as you remember unless it is almost time for your next dose, then skip the missed dose. · Avoid aspirin doses higher than 100 mg per day unless directed by your doctor. · Report any unusual bleeding, bruising, or blood in stool or urine immediately. · Do not stop taking BRILINTA without talking to your doctor, as stopping increases the risk of heart attack or stroke. · Inform all healthcare providers that you are taking BRILINTA before any surgery or dental procedure. · Store at room temperature away from moisture and heat. |