Cangrelor is an injectable P2Y12 platelet inhibitor indicated as an adjunct to percutaneous coronary intervention (PCI) for reducing the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis in patients who have not been treated with a P2Y12 platelet inhibitor and are not receiving a glycoprotein IIb/IIIa inhibitor. Cangrelor is the only injectable P2Y12 inhibitor and is only administered during PCI. Following PCI, patients are transitioned to an oral P2Y12 inhibitor. Platelet inhibition occurs within 2 minutes of drug administration and returns to normal within 1 hour of discontinuation. Cangrelor was approved by the FDA in June 2015.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration.
-Cangrelor is for intravenous use only.
Intravenous Administration
Reconstitution:
-Reconstitute by adding 5 mL Sterile Water for Injection to a 50 mg cangrelor vial. Swirl gently until all material is dissolved. Do not mix vigorously. Allow foam to settle.
-Ensure contents of the vial are fully dissolved. Reconstituted solution should be clear and colorless or pale yellow.
-Withdraw contents of one reconstituted 50 mg vial and add to one 250 mL bag of 0.9% Sodium Chloride Injection or Dextrose 5% Injection resulting in a final infusion concentration of 200 mcg/mL.
-One bag should be sufficient for most patients for at least 2 hours of dosing. Patients weighing more than 100 kg will require a minimum of 2 bags.
-Administer diluted cangrelor immediately. When stored at room temperature, diluted cangrelor is stable for up to 12 hours in Dextrose 5% Injection and 24 hours in 0.9% Sodium Chloride Injection.
Intravenous Administration:
-Administer cangrelor via a dedicated IV line.
-Bolus injection should be administered rapidly (< 1 minute). The bolus volume may be withdrawn from the diluted infusion bag and administered via manual IV push or may be administered via infusion pump.
-Ensure the bolus dose is completely administered prior to start of percutaneous coronary intervention (PCI).
-Start the continuous IV infusion immediately after administration of the bolus; an infusion pump should be used for the continuous IV infusion.
During cangrelor clinical trials, worsening renal function was reported in 3.2% of patients with severe renal impairment (creatinine clearance < 30 mL/minute) compared to 1.4% of clopidogrel patients with severe renal impairment.
Although not statistically significant, bleeding was reported at a higher incidence in the cangrelor group (15.5%) than clopidogrel (10.9%) in the CHAMPION PHOENIX trial. Severe or life-threatening (e.g., intracranial bleeding or bleeding resulting in substantial hemodynamic compromise requiring treatment) was reported in 0.2% of patients receiving cangrelor compared to 0.1% of those in the clopidogrel group. Serious. moderate, or minor bleeding events such as cardiac tamponade, myocardial or ventricular rupture, hemorrhagic shock, GI bleeding, retroperitoneal bleeding, intraocular bleeding, and genitourinary tract bleeding (e.g., hematuria) were tracked during clinical trials. Moderate bleeding (bleeding which required blood transfusion for intervention) was reported in 0.4% of the cangrelor group compared to 0.2% in the clopidogrel group. Mild bleeding (bleeding that required intervention, but not transfusion), such as ecchymosis, hematoma, or oozing from catheter sites, was reported in 14.9% of patients receiving cangrelor compared to 10.5% of those receiving clopidogrel.
During cangrelor clinical trials, hypersensitivity reactions including anaphylactoid reactions, anaphylactic shock, bronchospasm, angioedema, and wheezing/stridor were reported.
During cangrelor clinical trials, dyspnea was reported more often in patients receiving cangrelor than control (1.3% vs. 0.4%).
Cangrelor is contraindicated in patients with a known cangrelor hypersensitivity (e.g., anaphylaxis) or hypersensitivity to any component of the product.
Cangrelor is contraindicated in patients with significant active bleeding. Cangrelor increases the risk of bleeding. In clinical studies, the use of cangrelor was associated with a higher incidence of bleeding compared to clopidogrel. After discontinuation of cangrelor infusion, the effect on platelet inhibition decreases rapidly and platelet function returns to normal within 1 hour.
Although cangrelor dose adjustments are not required for patients with renal impairment, decreased renal function has been reported in patients with severe renal impairment (creatinine clearance < 30 mL/minute).
There are no available data on cangrelor use in human pregnancy to assess for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, continuous infusion of cangrelor throughout organogenesis at a dose approximately 2 times the maximum recommended human dose (MRHD) did not result in any fetal malformations. In rat studies, dose-related fetal growth retardation, characterized by increased incidences of incomplete ossification and unossified hind limb metatarsals, was observed at doses of 3 mcg/kg/minute or more. In rabbit studies, increased abortion and intrauterine loss were observed at doses of 12 mcg/kg/minute or more (3 times the MRHD). Fetal growth retardation, characterized by decreased fetal weights, slight reduction in ossification, and a slight increase in skeletal variants, was observed at 36 mcg/kg/minute (9 times the MRHD). Cangrelor did not produce malformations in embryofetal development studies and is not considered to be a teratogen. Cangrelor use during labor and obstetric delivery may increase the risk for maternal bleeding and hemorrhage. Performance of neuraxial blockade procedures is not recommended during cangrelor use due to the potential risk of spinal hematoma. When possible, discontinue use of cangrelor 1 hour prior to labor, delivery, or neuraxial blockade. Myocardial infarction is a medical emergency, which can be fatal to the pregnant woman and the fetus if left untreated. Do not withhold life-sustaining therapy due to the potential concerns about the effect of cangrelor on the fetus.
There are no data available on the presence of cangrelor in human or animal milk, the effects on the breast-fed infant, or the effects on milk production. However, due to its short half-life, cangrelor exposure is expected to very low in a breast-feeding infant.
Cangrelor has not been studied in pediatric patients. Safety and efficacy have not been established in adolescents, children, or infants.
General dosing information
Bridging from an oral P2Y12 inhibitor to intravenous cangrelor: Consider platelet function testing to determine time to initiate cangrelor infusion.
-Bridging from clopidogrel:
--Discontinue clopidogrel and initiate cangrelor 0.75 mcg/kg/minute (without a bolus dose) 2 to 3 days after the last administered clopidogrel dose.
-Bridging from prasugrel:
--Discontinue prasugrel and initiate cangrelor 0.75 mcg/kg/minute (without a bolus dose) 3 to 4 days after the last administered prasugrel dose.
-Bridging from ticagrelor:
--Discontinue ticagrelor and initiate cangrelor 0.75 mcg/kg/minute (without a bolus dose) 2 to 3 days after the last administered ticagrelor dose.
Switching from intravenous cangrelor to an oral P2Y12 inhibitor:
-Switching to clopidogrel:-Discontinue cangrelor and immediately administer clopidogrel 600 mg PO loading dose, then clopidogrel 75 mg PO once daily.
-Switching from prasugrel:-Discontinue cangrelor and immediately administer prasugrel 60 mg PO loading dose, then prasugrel 10 mg PO once daily.
-Switching from ticagrelor:-Administer ticagrelor 180 mg PO loading dose at any time during cangrelor infusion or immediately after infusion discontinuation, then ticagrelor 90 mg PO twice daily.
For percutaneous coronary intervention (PCI) as an adjunct to reduce the risk of periprocedural myocardial infarction (i.e., myocardial infarction prophylaxis), repeat coronary revascularization, and stent thrombosis in persons who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor:
Intravenous dosage:
Adults: 30 mcg/kg IV bolus before PCI, followed 4 mcg/kg/minute continuous IV infusion for at least 2 hours or the duration of PCI, whichever is longer. Transition to an oral P2Y12 platelet inhibitor after cangrelor discontinuation to maintain platelet inhibition.
Maximum Dosage Limits:
-Adults
30 mcg/kg IV bolus; 4 mcg/kg/minute IV infusion.
-Geriatric
30 mcg/kg IV bolus; 4 mcg/kg/minute IV infusion.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Not indicated.
-Neonates
Not indicated.
Patients with Hepatic Impairment Dosing
Because the metabolism of cangrelor is not dependent on hepatic function, no dosage adjustment is required for patients with hepatic impairment.
Patients with Renal Impairment Dosing
No dosage adjustment is required for patients with mild, moderate, or severe renal impairment.
*non-FDA-approved indication
Abrocitinib: (Contraindicated) Concurrent use with cangrelor is contraindicated during the first 3 months of abrocitinib therapy due to an increased risk of bleeding with thrombocytopenia.
Caplacizumab: (Major) Avoid concomitant use of caplacizumab and cangrelor when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Citalopram: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Clopidogrel: (Major) Do not administer clopidogrel until the cangrelor infusion is discontinued. The expected antiplatelet effect of a 600 mg loading dose of clopidogrel will be blocked if administered during the cangrelor infusion. Clopidogrel therapy should be initiated immediately after cangrelor discontinuation.
Defibrotide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like cangrelor is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Escitalopram: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Fluoxetine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Fluvoxamine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Olanzapine; Fluoxetine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Paroxetine: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Prasugrel: (Major) Do not administer prasugrel until the cangrelor infusion is discontinued. The expected antiplatelet effect of a 60 mg loading dose of prasugrel will be blocked if administered during the cangrelor infusion. Prasugrel therapy should be initiated immediately after cangrelor discontinuation.
Selective serotonin reuptake inhibitors: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Sertraline: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.
Cangrelor is a direct competitive inhibitor of the P2Y12 platelet receptor. Inhibition of the PY12 receptor prevents further signaling and platelet activation and thus results in inhibition of platelet activation and aggregation. In contrast to clopidogrel or prasugrel, cangrelor does not require hepatic conversion to an active metabolite.
Cangrelor is administered intravenously. Cangrelor is approximately 97% protein bound and undergoes rapid deactivation in the circulation by dephosphorylation to its inactive metabolite. Hepatic enzymes are not involved in the metabolism of cangrelor. The majority of cangrelor is excreted in urine. The average terminal half-life is 3-6 minutes.
Platelet inhibition occurs within 2 minutes after administration of a cangrelor 30 mcg/kg IV bolus followed by a 4 mcg/kg/minute IV infusion. Platelet inhibition is maintained throughout the duration of the infusion. After discontinuation of the cangrelor infusion, the anti-platelet effect decreases rapidly and platelet function returns to normal within 1 hour.
-Route-Specific Pharmacokinetics
Intravenous Route
Cangrelor follows linear pharmacokinetics. It is rapidly distributed and metabolized. The maximum plasma concentration is achieved within 2 minutes after administration of an intravenous (IV) bolus followed by IV infusion.
-Special Populations
Hepatic Impairment
Pharmacokinetic parameters of cangrelor are not affected by hepatic function.
Renal Impairment
Pharmacokinetic parameters of cangrelor are not affected by renal function.
Geriatric
Pharmacokinetic parameters of cangrelor are not affected by age.
Gender Differences
Pharmacokinetic parameters of cangrelor are not affected by gender.
Obesity
Although clearance of cangrelor is higher in obese patients, the impact of weight on drug exposure is accounted for by using weight-based dosing.