Ticagrelor, like other antiplatelet agents, can cause significant, sometimes fatal, bleeding.
Do not use ticagrelor in patients with active pathological bleeding or a history of intracranial hemorrhage.
Do not start ticagrelor in patients undergoing urgent coronary artery bypass graft surgery.
If possible, manage bleeding without discontinuing ticagrelor. Stopping ticagrelor increases the risk of subsequent cardiovascular events.
Maintenance doses of aspirin >100 mg daily reduce the effectiveness of ticagrelor and should be avoided.
Note: Efficacy: Concurrent aspirin maintenance dose should not exceed 100 mg/day. Safety: Use with caution or avoid use in patients at increased risk for bradycardic events. In patients who require concomitant therapeutic anticoagulation, antiplatelet selection and/or duration of therapy may differ in order to balance risks for thrombosis and bleeding (ACC [Kumbhani 2021]).
Acute coronary syndrome:
ST-elevation myocardial infarction:
Percutaneous coronary intervention, primary:
Loading dose: Oral: 180 mg once as early as possible after diagnosis in combination with aspirin and a parenteral anticoagulant; followed by maintenance dose (ACCF/AHA [O'Gara 2013]; Wallentin 2009).
Maintenance dose: Oral:
First 12 months after diagnosis: 90 mg twice daily beginning ~12 hours after the initial loading dose in combination with aspirin (ACCF/AHA [O'Gara 2013]; Wallentin 2009).
After 12 months from diagnosis: Reduce maintenance dose to 60 mg twice daily in combination with aspirin; in selected patients with ongoing high ischemic risk, may continue 90 mg twice daily in combination with aspirin. Also see "Duration of Therapy" below (Bonaca 2015; Bonaca 2016; Storey 2016).
Post-fibrinolysis:
Note: If fibrinolysis is chosen for reperfusion, it is recommended to administer clopidogrel (instead of ticagrelor) in combination with the fibrinolytic, aspirin, and a parenteral anticoagulant as soon as possible after diagnosis; subsequently, in patients <75 years of age, may transition from clopidogrel to ticagrelor (ACCF/AHA [O'Gara 2013]; Berwanger 2018; Berwanger 2019).
Loading dose: Oral: 180 mg once ≥12 hours after administration of fibrinolytic therapy (regardless of whether clopidogrel was co-administered at the time of diagnosis); followed by maintenance dose (Berwanger 2018; Berwanger 2019; Lincoff 2021).
Maintenance dose: Oral:
First 12 months after diagnosis: 90 mg twice daily beginning ~12 hours after the initial loading dose in combination with aspirin (ACCF/AHA [O'Gara 2013]; Wallentin 2009).
After 12 months from diagnosis: Reduce maintenance dose to 60 mg twice daily in combination with aspirin; in selected patients with ongoing high ischemic risk, may continue 90 mg twice daily in combination with aspirin. Also see "Duration of Therapy" below (Bonaca 2015; Bonaca 2016; Storey 2016).
No reperfusion:
Loading dose: Oral: 180 mg once as early as possible after diagnosis in combination with aspirin and a parenteral anticoagulant; followed by maintenance dose (ACCF/AHA [O'Gara 2013]; Wallentin 2009).
Maintenance dose: Oral:
First 12 months after diagnosis: 90 mg twice daily beginning ~12 hours after the initial loading dose in combination with aspirin (ACCF/AHA [O'Gara 2013]; Wallentin 2009).
After 12 months from diagnosis: Reduce maintenance dose to 60 mg twice daily in combination with aspirin; in selected patients with ongoing high ischemic risk, may continue 90 mg twice daily in combination with aspirin. Also see "Duration of Therapy" below (Bonaca 2015; Bonaca 2016; Storey 2016).
Duration of therapy: Continue ticagrelor plus aspirin (dual antiplatelet therapy [DAPT]) for ≥12 months unless major bleeding is a concern. If there have been no major bleeding complications within initial 12 months, continuation of DAPT may be considered. Reevaluate the need for DAPT at regular intervals based on bleeding and thrombotic risks. When DAPT is complete, discontinue ticagrelor and continue aspirin indefinitely (ACC/AHA [Levine 2016]; ACCF/AHA [O'Gara 2013]; Bonaca 2015; Wallentin 2009).
Non-ST-elevation acute coronary syndromes:
Note: The following dosing recommendations are the same whether reperfusion with percutaneous coronary intervention (PCI) is planned or no reperfusion is planned.
Loading dose: Oral: 180 mg once as early as possible after diagnosis in combination with aspirin and a parenteral anticoagulant; followed by maintenance dose (AHA/ACC [Amsterdam 2014]; Wallentin 2009).
Maintenance dose: Oral:
First 12 months after diagnosis: 90 mg twice daily beginning ~12 hours after the initial loading dose in combination with aspirin (AHA/ACC [Amsterdam 2014]; Wallentin 2009).
After 12 months from diagnosis: Reduce maintenance dose to 60 mg twice daily in combination with aspirin. In selected patients with ongoing high ischemic risk, may continue 90 mg twice daily in combination with aspirin. Also see “Duration of Therapy” below (Bonaca 2015; Bonaca 2016; Storey 2016).
Duration of therapy: Continue ticagrelor plus aspirin (DAPT) for ≥12 months unless major bleeding is a concern. If there have been no major bleeding complications within initial 12 months, continuation of DAPT may be considered. Reevaluate the need for DAPT at regular intervals based on bleeding and thrombotic risks. When DAPT is complete, discontinue ticagrelor and continue aspirin indefinitely (ACC/AHA [Levine 2016]; AHA/ACC [Amsterdam 2014]; Bonaca 2015; Wallentin 2009).
Coronary artery disease (stable) and high risk for ischemic cardiovascular events, primary prevention:
Note: Evaluate bleeding and thrombotic risks as well as patient preferences when considering dual antiplatelet therapy versus monotherapy with aspirin for primary prevention. Some experts recommend limiting use of dual antiplatelet therapy to patients with coronary artery disease and diabetes mellitus, at high risk for ischemic cardiovascular events, and at low risk for bleeding (Steg 2019).
Oral: 60 mg twice daily in combination with aspirin; continue ticagrelor and aspirin indefinitely (Steg 2019).
Minor ischemic stroke (NIHSS score ≤5) or high-risk transient ischemic attack (ABCD2 score ≥6):
Note: Short-term use of ticagrelor in combination with aspirin may be considered in patients who meet these criteria. Initiate antiplatelet therapy as soon as possible in the absence of contraindications. If an IV thrombolytic was administered, delay starting antiplatelet therapy for ≥24 hours but administer as soon as possible thereafter (Filho 2021; Johnston 2020).
Oral: Initial: 180 mg once in combination with aspirin, followed by 90 mg twice daily in combination with aspirin for 30 days (Johnston 2020).
Percutaneous coronary intervention for stable ischemic heart disease (off-label use):
Loading dose: Oral: 180 mg once prior to percutaneous coronary intervention in combination with aspirin and a parenteral anticoagulant; followed by a maintenance dose (Cutlip 2020c; Mehran 2019).
Maintenance dose: Oral: 90 mg twice daily beginning ~12 hours after the initial loading dose in combination with aspirin (Cutlip 2020c; Mehran 2019).
Duration of therapy: Continue ticagrelor plus aspirin for 3 months; after 3 months, discontinue aspirin and continue ticagrelor 90 mg twice daily for ≥1 year (Mehran 2019). When ticagrelor is discontinued, switch back to aspirin indefinitely (Cutlip 2021b).
Transitioning between P2Y12 inhibitors:
Note: This provides general guidance on transitioning between P2Y12 inhibitors.
Transitioning from another P2Y12 inhibitor to ticagrelor:
Transitioning from clopidogrel:
≤30 days after acute coronary syndrome (ACS) or PCI: Administer ticagrelor 180 mg loading dose once within 24 hours after the last dose of clopidogrel (irrespective of timing of previous clopidogrel dose), followed by 90 mg twice daily beginning 12 hours later (Angiolillo 2017; Cutlip 2021a; Lincoff 2021; Wallentin 2009).
>30 days after ACS or PCI: Administer ticagrelor 90 mg twice daily beginning 24 hours after the last dose of clopidogrel (Angiolillo 2017; Bonaca 2015; Gurbel 2010). Note: Some experts administer a ticagrelor 180 mg loading dose once within 24 hours after the last dose of clopidogrel (irrespective of timing of previous clopidogrel dose), followed by 90 mg twice daily beginning 12 hours later (Cutlip 2021a; Lincoff 2021).
Transitioning from prasugrel:
≤30 days after ACS or PCI: Administer ticagrelor 180 mg loading dose once within 24 hours after the last dose of prasugrel (irrespective of timing of previous prasugrel dose), followed by 90 mg twice daily beginning 12 hours later (Angiolillo 2017; Cutlip 2021a; Franchi 2016; Lincoff 2021).
>30 days after ACS or PCI: Administer ticagrelor 90 mg twice daily beginning 24 hours after the last dose of prasugrel (Angiolillo 2017; Franchi 2016). Note: Some experts administer a ticagrelor 180 mg loading dose once within 24 hours after the last dose of prasugrel (irrespective of timing of previous prasugrel dose), followed by 90 mg twice daily beginning 12 hours later (Cutlip 2021a; Lincoff 2021).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Butler 2012b; manufacturer's labeling).
Hemodialysis, intermittent (thrice weekly): Not dialyzed: No supplemental dose or dosage adjustment necessary (Teng 2018; manufacturer's labeling). A retrospective analysis of dialysis patients who had undergone percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) showed no difference in cardiovascular end points or bleeding for ticagrelor compared to clopidogrel (Lee 2019); however, patients with end-stage kidney disease (ESKD) are at increased risk for bleeding, with or without antiplatelet therapy (Huang 2014; Lee 2019; Tanios 2015); monitor closely.
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound): No dosage adjustment necessary (expert opinion). A retrospective analysis of dialysis patients who had undergone PCI for AMI showed no difference in cardiovascular end points or bleeding for ticagrelor compared to clopidogrel (Lee 2019); however, patients with ESKD are at increased risk for bleeding, with or without antiplatelet therapy (Huang 2014; Lee 2019; Tanios 2015); monitor closely.
CRRT: No dosage adjustment necessary (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).
Mild impairment: No dosage adjustment necessary.
Moderate impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, undergoes hepatic metabolism; use caution.
Severe impairment: Avoid use.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Brilinta: 60 mg, 90 mg
No
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Brilinta: 60 mg, 90 mg
An FDA-approved patient medication guide, which is available with the product information and at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/022433s031lbl.pdf#page=34, must be dispensed with this medication.
Oral: Administer with or without food. Missed doses should be taken at their next regularly scheduled time. For patients unable to swallow whole, tablets may be crushed and mixed with water to create a suspension for oral or NG (CH8/Fr8 or greater according to the manufacturer) use. If suspension is administered orally, refill glass with water, stir and drink; if administered via NG tube, flush NG tube through with water after administration (Crean 2013; Parodi 2015). Administration of crushed tablets, while bioequivalent to administration of whole tablets, may result in increased concentrations of ticagrelor and the major active metabolite at earlier time points (Teng 2015).
Acute coronary syndrome: To reduce the risk of cardiovascular death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of MI. Ticagrelor also reduces the risk of stent thrombosis in patients who have been stented for treatment of ACS.
Coronary artery disease (stable) and high risk for ischemic cardiovascular events, primary prevention: To reduce the risk of first MI or stroke in patients with coronary artery disease at high risk for such events. Note: Efficacy was established in patients with type 2 diabetes mellitus (Steg 2019), but the manufacturer does not limit use to this setting.
Minor ischemic stroke (NIHSS score ≤5) or high-risk transient ischemic attack (ABCD2 score ≥6): To reduce the risk of stroke in patients who meet these criteria.
Percutaneous coronary intervention for stable ischemic heart disease
Brilinta may be confused with Brintellix.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As with all drugs which may affect hemostasis, bleeding is associated with ticagrelor. Hemorrhage may occur at virtually any site. Risk is dependent on multiple variables, including the concurrent use of multiple agents which alter hemostasis and patient susceptibility.
>10%: Respiratory: Dyspnea (14% to 21%)
1% to 10%:
Cardiovascular: ECG abnormality (ventricular pause: 2% to 6%)
Endocrine & metabolic: Gout (≤2%)
Gastrointestinal: Nausea (4%)
Hematologic & oncologic: Major hemorrhage (4%), minor hemorrhage (4%)
Nervous system: Dizziness (5%)
Renal: Increased serum creatinine (7%; transient; mechanism undetermined)
Frequency not defined: Endocrine & metabolic: Increased uric acid
Postmarketing:
Cardiovascular: Atrioventricular block, bradycardia
Dermatologic: Skin rash
Hematologic & oncologic: Thrombotic thrombocytopenic purpura (Wang 2018)
Hypersensitivity: Angioedema, hypersensitivity reaction
Nervous system: Sleep apnea (central; Paboeuf 2019)
Respiratory: Cheyne-Stokes respiration
Miscellaneous: Laboratory test abnormality (false negative platelet functional tests, including heparin-induced platelet aggregation [HIPA] assay)
Hypersensitivity (eg, angioedema) to ticagrelor or any component of the formulation; active pathological bleeding (eg, peptic ulcer, intracranial hemorrhage); history of intracranial hemorrhage
Canadian labeling: Additional contraindications (not in US labeling): Moderate to severe hepatic impairment; concomitant use of strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, ritonavir, atazanavir, nefazodone)
Concerns related to adverse effects:
• Bleeding: [US Boxed Warning]: Ticagrelor increases the risk of bleeding including significant and sometimes fatal bleeding. Use is contraindicated in patients with active pathological bleeding (eg, peptic ulcer bleeding, intracranial hemorrhage) or history of intracranial hemorrhage. Additional risk factors for bleeding include propensity to bleed (eg, recent trauma or surgery, recent or recurrent GI bleeding, active peptic ulcer disease (PUD), moderate to severe hepatic impairment), coronary artery bypass graft (CABG) or other surgical procedure, concomitant use of medications that increase risk of bleeding (eg, warfarin, nonsteroidal anti-inflammatory drugs), and advanced age. Bleeding should be suspected if patient becomes hypotensive after undergoing recent coronary angiography, percutaneous coronary intervention, CABG, or other surgical procedure even if overt signs of bleeding do not exist. Where possible, manage bleeding without discontinuing ticagrelor because the risk of cardiovascular events is increased upon discontinuation. If discontinuation of ticagrelor is necessary, resume as soon as possible after the bleeding source is identified and controlled. Hemostatic benefits of platelet transfusions are not known; may inhibit transfused platelets.
• Bradyarrhythmias: Ventricular pauses and bradyarrhythmias, including atrioventricular (AV) block, have been reported. Use with caution or avoid in patients with second- or third-degree AV block, sick sinus syndrome, bradycardia-related syncope not protected by a pacemaker. Ventricular pauses ≥3 seconds were noted more frequently with ticagrelor than with clopidogrel during the first week after hospitalization for acute coronary syndrome (ACS) in a substudy of the Platelet Inhibition and Patient Outcomes (PLATO) trial; however, most ventricular pauses were asymptomatic and transient (Scirica 2011).
• Hyperuricemia: Use with caution in patients with a history of hyperuricemia or gouty arthritis. Renal uptake and transport of uric acid are inhibited by ticagrelor and its active metabolite and the risk of hyperuricemia may be increased (Butler 2012a; Zhang 2015). However, reports of gout did not differ between treatment groups in the PLATO trial.
• Respiratory: Dyspnea (often mild to moderate and transient) was observed more frequently in patients receiving ticagrelor compared to clopidogrel or aspirin alone during clinical trials (14% to 19% vs 6% to 8%) (Bonaca 2015; Wallentin 2009). Resolution of dyspnea was observed within 1 week in most patients (Wallentin 2009). Patients with new, prolonged, or worsening dyspnea should be evaluated to rule out underlying disease. Ticagrelor-related dyspnea does not require specific treatment nor does it warrant therapy interruption; however, therapy should be discontinued in patients unable to tolerate ticagrelor-related dyspnea.
• Sleep apnea: Central sleep apnea (CSA), including Cheyne-Stokes respiration, may occur, including recurrence or worsening with ticagrelor rechallenge. Further clinical assessment may be needed in patients who develop CSA.
• Thrombotic thrombocytopenic purpura: Cases of thrombotic thrombocytopenic purpura, some fatal, have been reported with ticagrelor; urgent treatment is required. Plasmapheresis should be considered (Doğan 2017; Wang 2018).
Disease-related concerns:
• Bleeding disorders: Use with caution in patients with platelet disorders, bleeding disorders, and/or at increased risk for bleeding (eg, PUD, trauma, surgery).
• Heparin-induced thrombocytopenia: False-negative results may occur for platelet activation functional assays, which are used to diagnose heparin-induced thrombocytopenia. This may be due to ticagrelor inhibition of P2Y12 receptors on healthy donor platelets, which are used for the assay, reducing platelet activation and interfering with results.
• Hepatic impairment: Use with caution in patients with moderate hepatic impairment (limited experience); avoid use in severe hepatic impairment (has not been studied).
• Renal impairment: Creatinine levels may rise during therapy (mechanism undetermined); monitor renal function.
Concurrent drug therapy issues:
• Aspirin/other NSAIDs: [US Boxed Warning]: Maintenance doses of aspirin >100 mg/day in patients with ACS reduce the efficacy of ticagrelor and should be avoided. Use of higher maintenance doses of aspirin (ie, >100 mg/day) was associated with relatively unfavorable outcomes for ticagrelor versus clopidogrel in the PLATO trial (Gaglia 2011; Wallentin 2009).
Special populations:
• Acute ischemic stroke/transient ischemic attack patients: Use is not recommended in acute ischemic stroke or transient ischemic attack patients with an NIHSS score >5 or patients receiving thrombolysis; not studied.
• Lower GI bleed patients: An individualized and multidisciplinary approach should be utilized to determine therapy discontinuation and management in patients with acute lower GI bleed who are on antiplatelet medications; risk of ongoing bleeding should be weighed with risk of thromboembolic events. In patients receiving dual antiplatelet therapy (aspirin plus P2Y12 receptor blocker [eg, clopidogrel, prasugrel, ticagrelor, ticlopidine]) or thienopyridine monotherapy, the thienopyridine should generally be resumed as soon as possible and at least within 7 days, taking into account control of bleeding and cardiovascular risk (aspirin should not be discontinued); however, dual antiplatelet therapy should not be discontinued in the 90 days post-acute coronary syndrome or 30 days post-coronary stenting (Strate 2016).
• Surgical patients: [US Boxed Warning]: Avoid initiation of ticagrelor when urgent CABG surgery is planned; when possible, discontinue use ≥5 days before any surgery. Discontinue therapy 5 days before elective surgery (except in patients with cardiac stents who have not completed their full course of dual antiplatelet therapy; patient-specific situations need to be discussed with cardiologist) (ACCF/AHA [Hillis 2011]). The American College of Cardiology Foundation/American Heart Association ST-elevation myocardial infarction guidelines recommend discontinuation for at least 24 hours prior to on-pump CABG if possible; off-pump CABG may be performed within 24 hours of ticagrelor administration if the benefits of prompt revascularization outweigh the risks of bleeding (ACCF/AHA [O’Gara 2013]). Elective noncardiac surgery should not be performed in patients in whom dual antiplatelet therapy (DAPT) will need to be discontinued perioperatively within 30 days following bare metal stent (BMS) placement or within 12 months after drug-eluting stent (DES) placement. In patients undergoing urgent noncardiac surgery during the first 4 to 6 weeks after BMS or DES placement, continue DAPT. In patients with stents undergoing surgery that requires discontinuation of the P2Y12 inhibitor (eg, ticagrelor), continue aspirin and restart the P2Y12 inhibitor as soon as possible after surgery (ACC/AHA [Fleisher 2014]).
Other warnings/precautions:
• Discontinuation of therapy: Premature discontinuation of therapy will increase the risk of myocardial infarction, stroke, and death in patients being treated for coronary artery disease. If ticagrelor must be discontinued (eg, treatment of bleeding, for significant surgery), restart ticagrelor as soon as possible. Duration of therapy, in general, is determined by the type of stent placed (bare metal or drug eluting) and whether an ACS event was ongoing at the time of placement.
Substrate of CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Abrocitinib: Agents with Antiplatelet Properties may enhance the antiplatelet effect of Abrocitinib. Management: Do not use antiplatelet drugs with abrocitinib during the first 3 months of abrocitinib therapy. The abrocitinib prescribing information lists this combination as contraindicated. This does not apply to low dose aspirin (81 mg/day or less). Risk X: Avoid combination
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Risk C: Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Apixaban: Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Apixaban. Specifically, the risk for bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk D: Consider therapy modification
Aspirin: May enhance the antiplatelet effect of Ticagrelor. Aspirin may diminish the therapeutic effect of Ticagrelor. More specifically, the benefits of ticagrelor relative to clopidogrel may be diminished in adult patients receiving daily aspirin doses greater than 100-150 mg daily. Management: Avoid daily aspirin doses greater than 100 mg in adults receiving ticagrelor. Canadian recommendations are to avoid adult daily aspirin doses greater than 150 mg. Daily low-dose aspirin (U.S.: 75-100 mg; Canada: 75-150 mg) is recommended. Risk D: Consider therapy modification
Atorvastatin: Ticagrelor may increase the serum concentration of Atorvastatin. Risk C: Monitor therapy
Bemiparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Bemiparin. Management: Avoid concomitant use of bemiparin with antiplatelet agents. If concomitant use is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
Collagenase (Systemic): Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Collagenase (Systemic). Specifically, the risk of injection site bruising and or bleeding may be increased. Risk C: Monitor therapy
CycloSPORINE (Systemic): May increase the serum concentration of Ticagrelor. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Moderate) may decrease the serum concentration of Ticagrelor. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inducers (Strong) may decrease the serum concentration of Ticagrelor. Risk X: Avoid combination
CYP3A4 Inhibitors (Moderate): May decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Moderate) may increase the serum concentration of Ticagrelor. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May decrease serum concentrations of the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the serum concentration of Ticagrelor. Risk X: Avoid combination
Dabigatran Etexilate: Ticagrelor may enhance the anticoagulant effect of Dabigatran Etexilate. Ticagrelor may increase the serum concentration of Dabigatran Etexilate. Management: Carefully consider the anticipated risks and benefits of this combination. Increase monitoring bleeding if these agents are combined and consider avoiding the use of this combination in the presence of reduced renal function. Risk D: Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Deoxycholic Acid: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Deoxycholic Acid. Specifically, the risk for bleeding or bruising in the treatment area may be increased. Risk C: Monitor therapy
Digoxin: Ticagrelor may increase the serum concentration of Digoxin. Risk C: Monitor therapy
Edoxaban: Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Edoxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider the anticipated risks and benefits of this combination. If combined, increased monitoring for bleeding is recommended. Risk D: Consider therapy modification
Enoxaparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Enoxaparin. Management: Discontinue antiplatelet agents prior to initiating enoxaparin whenever possible. If concomitant administration is unavoidable, monitor closely for signs and symptoms of bleeding. Risk D: Consider therapy modification
Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
FentaNYL: May diminish the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). FentaNYL may decrease the serum concentration of Antiplatelet Agents (P2Y12 Inhibitors). Risk C: Monitor therapy
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Ticagrelor. Risk C: Monitor therapy
Heparin: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Heparin. Management: Decrease the dose of heparin or agents with antiplatelet properties if coadministration is required. Risk D: Consider therapy modification
Herbal Products with Anticoagulant/Antiplatelet Effects (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Risk C: Monitor therapy
Ibritumomab Tiuxetan: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Ibritumomab Tiuxetan. Both agents may contribute to impaired platelet function and an increased risk of bleeding. Risk C: Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Icosapent Ethyl: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Ivosidenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lipid Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Lomitapide: Ticagrelor may increase the serum concentration of Lomitapide. Management: Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half with concurrent ticagrelor; the lomitapide dose may then be increased to a max adult dose of 30 mg/day (patients on lomitapide 5 mg/day may continue that dose). Risk D: Consider therapy modification
Lovastatin: Ticagrelor may increase the serum concentration of Lovastatin. Management: Limit lovastatin doses to 40 mg if coadministered with ticagrelor. Risk D: Consider therapy modification
Morphine (Systemic): May diminish the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). Morphine (Systemic) may decrease the serum concentration of Antiplatelet Agents (P2Y12 Inhibitors). Management: Consider alternative anti-ischemic/analgesic therapies (eg, beta-blockers, nitroglycerin) in patients with acute coronary syndromes treated with a P2Y12 inhibitor when possible. The risks associated with other opioids are unknown. Risk D: Consider therapy modification
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Obinutuzumab: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Obinutuzumab. Specifically, the risk of serious bleeding-related events may be increased. Risk C: Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Pentosan Polysulfate Sodium: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of bleeding may be increased by concurrent use of these agents. Risk C: Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Red Yeast Rice: Ticagrelor may increase the serum concentration of Red Yeast Rice. Management:Avoid using doses of red yeast rice greater than the equivalent of lovastatin 40 mg/day with ticagrelor. Monitor for increased systemic effects of lovastatin in patients receiving concurrent ticagrelor. Risk D: Consider therapy modification
Rivaroxaban: Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Rivaroxaban. Specifically, the risk of bleeding may be increased. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Risk D: Consider therapy modification
Rosuvastatin: Ticagrelor may enhance the adverse/toxic effect of Rosuvastatin. Risk C: Monitor therapy
Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Risk C: Monitor therapy
Selumetinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Simvastatin: Ticagrelor may increase the serum concentration of Simvastatin. Management: Avoid using doses of simvastatin greater than 40 mg/day with ticagrelor. Monitor for increased systemic effects of simvastatin in patients receiving concurrent ticagrelor. Risk D: Consider therapy modification
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Risk C: Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Risk X: Avoid combination
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Information related to the use of ticagrelor in pregnancy is limited (Verbruggen 2015).
Due to lack of data, use in pregnancy is not recommended (ESC [Regitz-Zagrosek 2018]).
It is not known if ticagrelor is present in breast milk.
Breastfeeding is not recommended by the manufacturer.
Signs of bleeding; hemoglobin and hematocrit periodically; sign/symptoms of bradycardia; renal function; uric acid levels (patients with gout or at risk of hyperuricemia); signs/symptoms of dyspnea.
Reversibly and noncompetitively binds the adenosine diphosphate (ADP) P2Y12 receptor on the platelet surface which prevents ADP-mediated activation of the GPIIb/IIIa receptor complex thereby reducing platelet aggregation. Due to the reversible antagonism of the P2Y12 receptor, recovery of platelet function is likely to depend on serum concentrations of ticagrelor and its active metabolite.
Onset of inhibition of platelet aggregation (IPA): 180 mg loading dose: ~41% within 30 minutes (similar to clopidogrel 600 mg at 8 hours)
Peak effect: Time to maximal IPA: 180 mg loading dose: IPA ~88% at 2 hours post administration
Duration of IPA: 180 mg loading dose: 87% to 89% maintained from 2 to 8 hours; 24 hours after the last maintenance dose, IPA is 58% (similar to maintenance dosing for clopidogrel)
Time after discontinuation when IPA is 30%: ~56 hours; IPA 10%: ~110 hours (Gurbel 2009). Mean IPA observed with ticagrelor at 3 days post-discontinuation was comparable to that observed with clopidogrel at 5 days post discontinuation.
Absorption: Rapid
Distribution: 88 L
Protein binding: >99% (parent drug and active metabolite)
Metabolism: Hepatic via CYP3A4/5 to active metabolite (AR-C124910XX)
Bioavailability: ~36% (range: 30% to 42%)
Half-life elimination: Parent drug: ~7 hours; active metabolite: ~9 hours
Time to peak:
Whole tablets: Parent drug: 1.5 hours (median; range: 1 to 4 hours); Active metabolite (AR-C124910XX): 2.5 hours (median; range: 1.5 to 5 hours)
Crushed tablets: Oral or nasogastric tube administration: Parent drug: ~1 hour (median; range: 1 to 4 hours); Active metabolite (AR-C124910XX): 2 hours (median; range: 1 to 8 hours). Note: Significantly higher concentrations of both ticagrelor and AR-C124910XX may appear at earlier time points (0.5 and 1 hour, respectively) when administered as crushed tablets (Teng 2015).
Excretion: Feces (58%); urine (26%); actual amount of parent drug and active metabolite excreted in urine was <1% of total dose administered
Renal function impairment: AUC and Cmax were 38% and 51% higher, respectively, in patients with end-stage renal disease on hemodialysis compared to patients with normal renal function following a single 90 mg dose of ticagrelor administered on a nondialysis day; similar exposure was observed when administered immediately prior to dialysis. Inhibition of platelet aggregation was independent of dialysis and similar to healthy adults with normal renal function.
Cigarette smoking: Mean clearance was increased by ~22% in smokers.
Tablets (Brilinta Oral)
60 mg (per each): $8.51
90 mg (per each): $8.51
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