Cangrelor (Monograph)

Brand name: Kengreal
Drug class: Platelet-aggregation Inhibitors
Chemical name: N-[2-(Methylthio)ethyl]-2-[(3,3,3-trifluoropropyl)thio]-5′-adenylic acid monoanhydride with (dichloromethylene)bis[phosphonic acid] tetrasodium salt
Molecular formula: C₁₇H₂₁Cl₂F₃N₅Na₄O₁₂P₃S₂
CAS number: 163706-36-3

Medically reviewed by Drugs.com on Dec 5, 2024. Written by ASHP.

Introduction

Platelet-activation and -aggregation inhibitor; nonthienopyridine, reversible, P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist. ^{1 2 6}

Uses for Cangrelor

Acute Ischemic Complications of PCI

Used as an adjunct to PCI to reduce the risk of periprocedural MI, repeat coronary revascularization, and stent thrombosis in patients who have not been treated with a P2Y12-receptor antagonist and are not being given a glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor.^{1 2}

Dual antiplatelet therapy with aspirin and a P2Y12 receptor inhibitor is considered the current standard of care in patients undergoing PCI.⁹⁹⁴

Cangrelor is the only currently available IV P2Y12 receptor inhibitor.²³ Compared with oral P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor), cangrelor has a rapid onset and offset of action; following an IV bolus dose, platelet inhibition is immediate and can be maintained with continuous IV infusion.^{2 27}

May be useful in patients who cannot take oral medications (e.g., intubated patients or those with shock, cardiac arrest, or nausea/vomiting) or patients who may benefit from a rapidly acting or reversible agent (e.g., those who have bleeding complications with PCI or are candidates for emergent invasive procedures such as CABG).^{9 10 11 18}

Cangrelor Dosage and Administration

General

• Intended to be given to patients prior to PCI in conjunction with other standard-of-care therapy (e.g., aspirin, anticoagulants).^{1 994}

Administration

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

Must reconstitute commercially available lyophilized powder and further dilute prior to administration.¹

Administer by rapid IV (“bolus”) injection (over <1 minute) from the prepared IV infusion bag via manual IV push or infusion pump, followed by IV infusion.^{1 9}

Reconstitution

Reconstitute vial containing 50 mg of lyophilized cangrelor with 5 mL of sterile water for injection (swirl gently).¹

Dilution

Dilute reconstituted solution in 250 mL of 5% dextrose or 0.9% sodium chloride injection to a final concentration of 200 mcg/mL.¹

Rate of Administration

Rapid IV (“bolus”) injection: Administer over <1 minute.¹

Continuous IV infusion: Administer for at least 2 hours or for duration of PCI, whichever is longer.^{1 2}

Dosage

Available as cangrelor tetrasodium; dosage expressed in terms of cangrelor.¹

Adults

Acute Ischemic Complications of PCI

IV

30 mcg/kg by rapid IV (“bolus”) injection prior to PCI, immediately followed by 4 mcg/kg per minute by continuous IV infusion for at least 2 hours or for the duration of the procedure, whichever is longer.^{1 2 13 14}

Transitioning to Oral Therapy

After discontinuance of cangrelor infusion, administer an oral P2Y12-receptor antagonist (clopidogrel, prasugrel, or ticagrelor) to maintain platelet inhibition.^{1 16 17}

If ticagrelor used, administer 180 mg any time during cangrelor infusion or immediately after discontinuance of the infusion.¹

If clopidogrel used, administer 600 mg immediately after discontinuance of cangrelor infusion; do not administer concurrently with cangrelor.¹ (See Specific Drugs under Interactions.)

If prasugrel used, administer 60 mg immediately after discontinuance of cangrelor infusion; do not administer concurrently with cangrelor.¹ (See Specific Drugs under Interactions.)

Special Populations

Renal Impairment

Dosage adjustment not required.¹

Hepatic Impairment

Dosage adjustment not required.¹

Cautions for Cangrelor

Contraindications

• Substantial active bleeding.¹

• Known hypersensitivity to cangrelor or any ingredient in the formulation.¹

Warnings/Precautions

Bleeding

Possible bleeding, especially hematoma at the site of vascular access.^{1 2 3 4 6 8 9 10 11} (See Contraindications.)

In pivotal clinical trial, greater incidence of bleeding events of all severities with cangrelor compared with clopidogrel; however, rate of severe bleeding (per the Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO] criteria) not substantially different between treatment groups.^{1 2 6}

Antiplatelet effect negligible 1 hour after discontinuance of cangrelor infusion.^{1 6 11 14 16 18}

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions (e.g., anaphylaxis, bronchospasm, angioedema, stridor) reported.¹ (See Contraindications.)

Specific Populations

Pregnancy

No adequate and well-controlled studies of cangrelor in pregnant women.¹ In animal studies, cangrelor produced dose-related fetal growth retardation and increased incidences of abortion and/or intrauterine losses, but did not produce malformations; not considered to be a teratogen.¹

Lactation

Not known whether cangrelor is distributed into human milk; discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established.^{1 2}

Geriatric Use

No substantial differences in safety or efficacy relative to younger adults.¹

Renal Impairment

No dosage adjustment required; however, worsening renal function reported in some patients with severe renal impairment (Cl_cr <30 mL/minute) receiving cangrelor in clinical studies.¹

Hepatic Impairment

Safety and efficacy not established in patients with hepatic impairment.¹ Hepatic impairment not expected to affect pharmacokinetics because metabolism not dependent on hepatic function.^{1 11}

Common Adverse Effects

Bleeding; transient dyspnea reported in some patients.^{1 2 3 4 16}

Drug Interactions

Drugs Metabolized by Hepatic Microsomal Enzymes

Neither cangrelor nor its major metabolites inhibit activity of the hepatic CYP isoenzymes at therapeutic concentrations in vitro.¹ Cangrelor not expected to interact with drugs metabolized by these microsomal enzymes.¹

Specific Drugs

Cangrelor Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations achieved within 2 minutes after administration of rapid IV (“bolus”) injection followed by continuous infusion.^{1 9}

Onset

Immediate antiplatelet effect.^{1 9}

Duration

Platelet function returns to normal within 1 hour after discontinuance of infusion.^{1 9 18}

Distribution

Extent

Not known whether the drug is distributed into human milk.¹

Plasma Protein Binding

Approximately 97–98%.¹

Elimination

Metabolism

Rapidly deactivated in circulation by dephosphorylation to its primary metabolite, which has negligible antiplatelet activity.^{1 9 11 16}

Elimination Route

Excreted in urine (58%) and feces (35%).^{1 11}

Half-life

3–6 minutes.^{1 6 11 14 16 18}

Special Populations

Pharmacokinetics not affected by gender, age, renal status, or hepatic function.^{1 11} Body weight has effect on pharmacokinetics but accounted for by weight-based infusion regimen.^{1 11}

Stability

Storage

Parenteral

Powder for Injection

20–25°C (may be exposed to 15–30°C).¹

Diluted IV solutions (200 mcg/mL) are stable at room temperature for up to 12 hours in 5% dextrose injection and 24 hours in 0.9% sodium chloride injection.¹

Compatibility

Parenteral

Solution Compatibility1

Actions

• Nonthienopyridine, direct-acting P2Y12 platelet ADP-receptor antagonist; unlike thienopyridines (e.g., clopidogrel, prasugrel), but like ticagrelor, cangrelor binds reversibly to P2Y12 receptor and does not require hepatic transformation to exert its pharmacologic effects.^{1 2 6 9 13}

• Prevents signal transduction of the cyclic adenosine monophosphate (cAMP) pathway, resulting in reduced exposure of fibrinogen binding sites to the GP IIb/IIIa complex and subsequent inhibition of platelet activation and aggregation.^{13 19}

• Compared with clopidogrel, cangrelor produces more rapid and effective inhibition of platelet aggregation and has a faster onset and offset of action.^{1 18 20}

Advice to Patients

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

• Importance of patients informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.¹

• Importance of informing patients of other important precautionary information.¹ (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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