Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Kengreal: 50 mg (1 ea)
Pharmacology
Mechanism of Action
Cangrelor, a nonthienopyridine adenosine triphosphate analogue, is a direct P2Y12 platelet receptor inhibitor that blocks adenosine diphosphate (ADP)-induced platelet activation and aggregation. Cangrelor binds selectively and reversibly to the P2Y12 receptor, preventing further signaling and platelet activation.
Pharmacokinetics/Pharmacodynamics
Distribution
Volume of distribution: 3.9 L
Metabolism
Rapidly inactivated in the circulation by dephosphorylation to its primary metabolite, a nucleoside, which has negligible anti-platelet activity
Excretion
Urine (58%); feces (35%)
Onset of Action
Platelet inhibition occurs within 2 minutes
Time to Peak
Within 2 minutes
Duration of Action
Antiplatelet effect is maintained throughout duration of infusion. After discontinuation, platelet function returns to normal within 1 hour
Half-Life Elimination
~3 to 6 minutes
Protein Binding
~97% to 98%
Use: Labeled Indications
Percutaneous coronary intervention (PCI): Adjunct to PCI to reduce 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 being given a glycoprotein IIb/IIIa inhibitor
Use: Off Label
Bridging therapy prior to cardiac surgeryb
Data from a multicenter, randomized, double blind study support the use of cangrelor following thienopyridine discontinuation in patients awaiting nonemergent coronary artery bypass graft surgery. Of note, ischemic endpoints were low in both the cangrelor and placebo groups Angiolillo 2012. Additional trials may be necessary to further define the role of cangrelor in this setting.
Contraindications
Known hypersensitivity (eg, anaphylaxis) to cangrelor or any component of the formulation; significant active bleeding
Dosage and Administration
Dosing: Adult
Percutaneous coronary intervention (PCI): IV: 30 mcg/kg bolus prior to PCI followed immediately by an infusion of 4 mcg/kg/minute continued for at least 2 hours or for the duration of the PCI, whichever is longer.
Transitioning patients to oral P2Y12 antagonist therapy after PCI:
Conversion to clopidogrel: Administer 600 mg of clopidogrel immediately after discontinuing cangrelor infusion. Do not administer clopidogrel prior to cangrelor discontinuation.
Conversion to prasugrel: Administer 60 mg of prasugrel immediately after discontinuing cangrelor infusion. Do not administer prasugrel prior to cangrelor discontinuation.
Conversion to ticagrelor: Administer 180 mg of ticagrelor at any time during cangrelor infusion or immediately after discontinuing cangrelor infusion.
Bridging therapy prior to cardiac surgery (off-label use): IV: 0.75 mcg/kg/min (without a bolus dose) following thienopyridine discontinuation for up to 7 days prior to surgery; discontinue 1 to 6 hours prior to surgical incision (Angiolillo 2012).
Dosing: Geriatric
Refer to adult dosing.
Reconstitution
Reconstitute 50 mg vial by adding 5 mL of Sterile Water for Injection. Swirl gently until dissolved (should be clear and colorless to pale yellow). Avoid vigorous mixing. Allow any foam to settle. Must be diluted prior to administration. Immediately after reconstitution, add the contents of one vial to 250 mL of NS or D5W; mix thoroughly. Resultant concentration of solution for infusion: 200 mcg/mL.
Patients ≥100 kg will require a minimum of 2 bags.
Administration
IV: Vial must be diluted prior to infusion. Administer via a dedicated IV line.
Obtain bolus volume from the prepared bag and administer rapidly over <1 minute via manual IV push or the infusion pump. Ensure the bolus is completely administered before the start of PCI. Start the infusion immediately after administration of the bolus.
Storage
Store at controlled room temperature between 20°C and 25°C (68°F and 77°F); excursions are permitted to 15°C to 30°C (59°F and 86°F). Solutions diluted for infusion are stable for up to 12 hours in D5W or 24 hours in NS at room temperature.
Drug Interactions
Acalabrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the antiplatelet effect of other Agents with Antiplatelet Properties. Monitor therapy
Anticoagulants: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Anticoagulants. Exceptions: Bemiparin; Enoxaparin; Heparin. 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. Consider therapy modification
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. Consider therapy modification
Cephalothin: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Cephalothin. Specifically, the risk for bleeding may be increased. Monitor therapy
Clopidogrel: Cangrelor may diminish the antiplatelet effect of Clopidogrel. More specifically, while the use of Cangrelor is expected to increase total platelet inhibition in patients who have previously received Clopidogrel, Cangrelor is expected to decrease binding of Clopidogrel metabolites to P2Y12 receptors and thus reduce the extent of irreversible platelet inhibition. Management: Avoid administration of clopidogrel until cangrelor infusion is discontinued. Consider therapy modification
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. Monitor therapy
Dabigatran Etexilate: Antiplatelet Agents (P2Y12 Inhibitors) may enhance the adverse/toxic effect of Dabigatran Etexilate. Specifically, the risk of bleeding may be increased. Antiplatelet Agents (P2Y12 Inhibitors) may increase the serum concentration of Dabigatran Etexilate. Specifically, clopidogrel may increase dabigatran serum concentrations. Management: Carefully consider risks and benefits of this combination and monitor closely; Canadian labeling recommends avoiding prasugrel or ticagrelor. Consider therapy modification
Dasatinib: May enhance the anticoagulant effect of Agents with Antiplatelet Properties. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. 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. 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. 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. Consider therapy modification
Fat Emulsion (Fish Oil Based): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy
FentaNYL: May diminish the antiplatelet effect of Antiplatelet Agents (P2Y12 Inhibitors). FentaNYL may decrease the serum concentration of Antiplatelet Agents (P2Y12 Inhibitors). Monitor therapy
Glucosamine: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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. Consider therapy modification
Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Bleeding may occur. Management: Avoid combination when possible. If used, monitor more closely for evidence of bleeding. Discontinue herbal products with anticoagulant or antiplatelet actions 2 weeks prior to surgical, dental, or invasive procedures. Consider therapy modification
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. Monitor therapy
Ibrutinib: May enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Monitor therapy
Inotersen: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Limaprost: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Fluoride (with ADE): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Minerals (with ADEK, Folate, Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Multivitamins/Minerals (with AE, No Iron): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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. Monitor therapy
Omega-3 Fatty Acids: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. 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. Monitor therapy
Pentoxifylline: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Prasugrel: Cangrelor may diminish the antiplatelet effect of Prasugrel. More specifically, while the use of Cangrelor is expected to increase total platelet inhibition in patients who have previously received Prasugrel, Cangrelor is expected to decrease binding of Prasugrel metabolites to P2Y12 receptors and thus reduce the extent of irreversible platelet inhibition. Management: Avoid administration of prasugrel until cangrelor is discontinued. Consider therapy modification
Prostacyclin Analogues: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
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. Consider therapy modification
Salicylates: Agents with Antiplatelet Properties may enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy
Thrombolytic Agents: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Thrombolytic Agents. Monitor therapy
Tipranavir: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Urokinase: Agents with Antiplatelet Properties may enhance the anticoagulant effect of Urokinase. Avoid combination
Vitamin E (Systemic): May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Zanubrutinib: May enhance the antiplatelet effect of Agents with Antiplatelet Properties. Monitor therapy
Adverse Reactions
Hematologic & oncologic: Hemorrhage (GUSTO: 16%; TIMI: <1%)
Renal: Renal insufficiency (3%; severe; creatinine clearance <30 mL/minute)
Respiratory: Dyspnea (1%)
<1%, postmarketing, and/or case reports: Hypersensitivity reaction
Warnings/Precautions
Concerns related to adverse effects:
- Bleeding: Similar to other P2Y12 antagonists, the use of cangrelor increases the risk of bleeding; however, due to the short elimination half-life, no antiplatelet effect is observed an hour after discontinuation.
- Hypersensitivity: Although rare, serious cases of hypersensitivity (eg, anaphylaxis, anaphylactic shock, bronchospasm, angioedema, stridor) have been reported with cangrelor.
Concurrent drug therapy issues:
- Thienopyridines: If clopidogrel or prasugrel are administered prior to discontinuation of the cangrelor infusion, no antiplatelet effect will occur until the next dose is administered. Therefore, do not administer until after the cangrelor infusion is discontinued.
Monitoring Parameters
Monitor for signs/symptoms of bleeding.
Pregnancy
Pregnancy Risk Factor
C
Pregnancy Considerations
Adverse events were observed in some animal reproduction studies.
Patient Education
What is this drug used for?
- It is used to lower the chance of heart attack, the need for some heart treatments, or blockage of a stent after a stent is placed in the heart.
- It may be given to you for other reasons. Talk with the doctor.
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.
- Severe cerebrovascular disease like change in strength on one side is greater than the other, trouble speaking or thinking, change in balance, or vision changes.
- Severe headache
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
