Cangrelor

Usage

• Cangrelor is prescribed as an adjunct to percutaneous coronary intervention (PCI) to minimize the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who haven’t received a P2Y12 platelet inhibitor and aren’t currently on a glycoprotein IIb/IIIa inhibitor.
• Pharmacological classification: Antiplatelet agent; P2Y12 receptor antagonist.
• Cangrelor reversibly binds to the P2Y12 receptor on platelets, preventing adenosine diphosphate (ADP) from binding and triggering platelet activation and aggregation, thus reducing blood clot formation.

Alternate Names

• Kengreal (US)
• Kengrexal (EU)

How It Works

• Pharmacodynamics: Cangrelor directly and reversibly binds to the P2Y12 receptor on platelets, inhibiting ADP-induced platelet activation and aggregation. This rapid and reversible effect provides immediate and adjustable platelet inhibition, minimizing the risk of ischemic events during PCI while allowing quick restoration of platelet function after the procedure.

• Pharmacokinetics:

  • Absorption: Administered intravenously, achieving rapid and complete bioavailability.
  • Metabolism: Rapidly metabolized by dephosphorylation to its inactive metabolite. Hepatic metabolism is not involved.
  • Elimination: Inactive metabolites are primarily excreted renally, with a small fraction excreted in the feces. The half-life is 3-6 minutes, leading to rapid restoration of platelet function within an hour of discontinuation.

• Mode of Action: Competitive antagonist at the platelet P2Y12 receptor. Cangrelor blocks ADP-induced activation of the GPIIb/IIIa receptor, a key mediator of platelet aggregation.

• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Competitive P2Y12 receptor antagonist; no known enzyme inhibition or neurotransmitter modulation.

• Elimination pathways: Renal excretion of inactive metabolites (primary route); minor fecal excretion. Not metabolized by CYP enzymes.

Dosage

Standard Dosage

Adults:

• 30 mcg/kg intravenous (IV) bolus administered over <1 minute immediately before PCI.
• Followed by a 4 mcg/kg/min continuous IV infusion for at least 2 hours or for the duration of the procedure, whichever is longer. The infusion can be continued for up to a maximum of 4 hours at the physician’s discretion.
• Transition to oral P2Y12 inhibitor therapy (clopidogrel 600mg, ticagrelor 180mg, or prasugrel 60mg) immediately upon Cangrelor discontinuation, or up to 30 min before discontinuation for ticagrelor or prasugrel (not clopidogrel).

Children:

• Safety and efficacy haven’t been established in children under 18 years.

Special Cases:

• Elderly Patients: No dose adjustment is required for elderly patients.

• Patients with Renal Impairment: No dose adjustment is necessary. Close monitoring is recommended.

• Patients with Hepatic Dysfunction: No dose adjustment is required as cangrelor does not involve hepatic metabolism.

• Patients with Comorbid Conditions: Exercise caution in patients with a history of bleeding diathesis or those receiving concomitant medications that increase the risk of bleeding.

Clinical Use Cases

Cangrelor’s primary clinical use is as an adjunct to PCI. Dosages are as per the standard adult recommendations, specifically timed to coincide with the PCI procedure: bolus before, followed by infusion for at least two hours or the duration of the procedure. Post-procedure, patients transition to oral P2Y12 inhibitors. Use in specific settings such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations outside the PCI context hasn’t been established.

Dosage Adjustments

• Dose adjustments aren’t required for renal/hepatic impairment, elderly patients, or specific metabolic disorders.

Side Effects

Common Side Effects

• Bleeding (ranging from minor bruising/nosebleeds to major hemorrhage)
• Dyspnea (shortness of breath)

Rare but Serious Side Effects

• Allergic reactions (anaphylaxis, bronchospasm, angioedema)
• Severe or life-threatening bleeding (intracranial hemorrhage, cardiac tamponade)
• Worsening of renal function in patients with pre-existing severe renal impairment (CrCl < 30mL/min)

Long-Term Effects

• No specific long-term side effects have been identified. As treatment is short-term, limited data on chronic effects exist.

Adverse Drug Reactions (ADR)

• Bleeding requiring transfusion
• Allergic reactions requiring urgent medical intervention (epinephrine, antihistamines, corticosteroids)
• Acute renal failure in patients with severe pre-existing renal impairment

Contraindications

• Active bleeding or increased bleeding risk (e.g., recent major surgery/trauma, coagulation disorders, uncontrolled severe hypertension).
• History of stroke or transient ischemic attack (TIA).
• Hypersensitivity to cangrelor or its components (mannitol, sorbitol, sodium hydroxide).

Drug Interactions

• Clopidogrel and Prasugrel: Do not co-administer with Cangrelor. Administer loading dose after Cangrelor discontinuation. Cangrelor decreases the effectiveness of these drugs by receptor binding competition.
• Ticagrelor: Can be administered up to 30 minutes before stopping Cangrelor.
• Other Antiplatelet Agents (besides low-dose aspirin ≤81mg/day): Should generally be avoided during cangrelor use due to increased bleeding risk.
• Anticoagulants: Concomitant use with anticoagulants (e.g., warfarin, heparin) may increase bleeding risk. Monitor closely if co-administration is necessary.
• CYP450 interactions: Cangrelor isn’t metabolized by CYP450 enzymes, minimizing the risk of CYP-mediated drug interactions.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (US FDA). Animal studies show potential for fetal harm, but there are no adequate and well-controlled studies in humans. Use only if potential benefit outweighs risk.
• Breastfeeding: Cangrelor’s presence in human milk is unknown. Discontinue breastfeeding or the drug, weighing the potential risks to the infant.

Drug Profile Summary

• Mechanism of Action: Reversible P2Y12 receptor antagonist, inhibiting ADP-induced platelet activation and aggregation.
• Side Effects: Bleeding (common), dyspnea, allergic reactions (rare).
• Contraindications: Active bleeding, stroke/TIA history, hypersensitivity.
• Drug Interactions: Clopidogrel, prasugrel (do not co-administer). Increased bleeding risk with other antiplatelet and anticoagulant medications.
• Pregnancy & Breastfeeding: Category C; not recommended unless potential benefits outweigh risk to fetus/neonate.
• Dosage: 30 mcg/kg IV bolus + 4 mcg/kg/min IV infusion for ≥2 hours or the procedure’s duration (max 4 hours).
• Monitoring Parameters: Bleeding signs, hemoglobin, platelet count, renal function (in patients with pre-existing renal impairment).

Popular Combinations

• Aspirin (low dose, ≤ 81mg/day) and heparin are commonly given with Cangrelor during PCI.
• Cangrelor is used as a bridge to oral P2Y12 inhibitors (clopidogrel, ticagrelor, prasugrel).

Precautions

• General Precautions: Assess for active bleeding, bleeding history, recent surgery/trauma, and hypersensitivity to cangrelor. Closely monitor for signs of bleeding during and after infusion. Ensure appropriate transition to oral antiplatelet therapy for long-term management.
• Specific Populations:
  • Pregnant Women: Weigh risks vs benefits if PCI is essential.
  • Breastfeeding Mothers: Discontinue breastfeeding or Cangrelor.
  • Children & Elderly: No dosage adjustments are needed.
  • Menstruating Individuals: Be aware of the increased potential for heavy menstrual bleeding.
• Lifestyle Considerations: Caution patients about activities that increase bleeding risk, such as strenuous exercise or using sharp objects.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Cangrelor?

A: 30 mcg/kg IV bolus followed by 4 mcg/kg/min IV infusion for ≥2 hours or duration of the procedure, whichever is longer (max 4 hours). Transition to oral P2Y12 inhibitor post-procedure.

Q2: How does Cangrelor differ from clopidogrel?

A: Cangrelor is an intravenous, reversible P2Y12 inhibitor offering rapid onset and offset, crucial for the PCI setting. Clopidogrel is an oral medication with a slower onset and irreversible binding, better suited for long-term management.

Q3: What is the mechanism of action of Cangrelor?

A: Cangrelor competitively and reversibly binds to platelet P2Y12 receptors, blocking ADP-induced platelet activation and aggregation.

Q4: What are the major side effects of Cangrelor?

A: Bleeding is the most common side effect. Rarely, hypersensitivity reactions and dyspnea can occur.

Q5: Can Cangrelor be used in patients with renal impairment?

A: Yes, no dosage adjustment is needed for renal impairment. Close monitoring is advised.

Q6: Is Cangrelor safe during pregnancy?

A: Cangrelor is a Pregnancy Category C drug. Use only if the potential benefits outweigh the potential risks to the fetus.

Q7: When should Cangrelor be discontinued before surgery?

A: Cangrelor’s rapid offset means platelet function is restored within one hour of discontinuation, so typically cessation 1-6 hours before surgery is considered, depending on the context and bleeding risk assessment.

Q8: How is Cangrelor administered?

A: Cangrelor is administered via intravenous bolus followed by continuous infusion, via a dedicated IV line. The medication requires reconstitution and dilution before administration.

Q9: What are the contraindications for using Cangrelor?

A: Active bleeding, history of stroke/TIA, hypersensitivity to cangrelor or its components.

Q10: How quickly are platelet levels restored after Cangrelor cessation?

A: Platelet function returns to normal within approximately one hour of discontinuing Cangrelor infusion.