Cangrelor

Cangrelor is an P2Y12 ADP receptor antagonist on platelets belonging to Antiplatelet Agent.

Cangrelor is a P2Y12 platelet receptor antagonist used during percutaneous coronary intervention to reduce the risk for periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST).

Cangrelor is rapidly distributed and metabolized, reaching Cmax within 2 minutes after administration of an intravenous bolus followed by infusion. In a study in healthy volunteers, Cangrelor administration at a dose of 30 mcg/kg bolus plus 4 mcg/kg/min showed a volume of distribution of 3.9 L. Plasma protein binding of Cangrelor is about 97-98%. Cangrelor is deactivated rapidly in the circulation by dephosphorylation to its primary metabolite, a nucleoside, which has negligible anti-platelet activity. Cangrelor metabolism is independent of hepatic function, and it does not interfere with other drugs metabolized by hepatic enzymes. Following IV administration of [3 H] Cangrelor 58% of radioactivity was recovered in urine. The remaining 35% of radioactivity was in feces, presumably following biliary excretion. The average elimination half-life of Cangrelor is about 3-6 minutes.

Cangrelor shows common side effects like Abdominal or stomach pain or swelling, back pain, black, tarry stools, blood in the eyes, blood in the urine, bruising or purple areas on the skin, coughing up blood, decreased alertness, dizziness, headache, joint pain or swelling, nosebleeds.

Cangrelor is available in Powder for Injection.

Cangrelor is available in India, US, Canada, Finland, Spain, Denmark, Austria, and Switzerland.

Cangrelor belonging to the Antiplatelet Agent, acts as an P2Y12 ADP receptor antagonist.

Cangrelor is a selective, reversible, P2Y12 platelet receptor antagonist which inhibits ADP platelet aggregation. ADP is typically released by damaged blood vessels, red blood cells, and/or platelets due to agonists stimulating platelet activity. ADP binds to P2Y12 to stimulate and complete platelet aggregation by inhibiting adenylyl cyclase by a Gi protein, thus potentiating dense granule secretion, and increasing coagulation activity. Cangrelor acts on the same target as oral irreversible inhibitors clopidogrel and ticlopidine and has a similar mechanism of action but is reversible and provides a fast onset and offset of action.

The Onset of action of Cangrelor is occurs within 2 minutes.

There is no well-established clinical data available regarding the duration of action of Cangrelor.

The Tmax of Cangrelor is approximately 2 minutes.

Cangrelor is available in the form of Powder for Injection.

Cangrelor powder for injection is given via intravenous route.

Cangrelor is a P2Y12 platelet receptor antagonist used during percutaneous coronary intervention to reduce the risk for periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST).

Cangrelor is an P2Y12 ADP receptor antagonist on platelets belonging to Antiplatelet Agent.

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.

Cangrelor is approved for use in the following clinical indications

• Percutaneous coronary intervention

Cangrelor is indicated as an adjunct to percutaneous coronary intervention (PCI) to reduce the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.

Although not approved, there have been certain off-label indications. These include

• Bridging therapy prior to cardiac surgery

• Percutaneous coronary intervention

IV: 30 mcg/kg bolus prior to percutaneous coronary intervention (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.

• 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 based on risk for thrombotic complications after antiplatelet therapy has been withheld.

Cangrelor is available in the form of Powder for Injection.

Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Cangrelor is contraindicated in patients with

• Significant Active Bleeding

Cangrelor is contraindicated in patients with significant active bleeding.

• Hypersensitivity

Cangrelor is contraindicated in patients with known hypersensitivity (e.g., anaphylaxis) to Cangrelor or any component of the product.

• 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.

There are no data on the presence of cangrelor in human milk or animal milk, the effects on the breastfed infant, or the effects on milk production. However, due to its short-half life, cangrelor exposure is expected to be very low in the breastfed infant.

There are no available data on cangrelor use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Untreated myocardial infarction can be fatal to the pregnant women and fetus. In animal reproduction studies, continuous infusion of cangrelor in pregnant rats and rabbits throughout organogenesis at dose approximately 2-times the maximum recommended human dose (MRHD) did not result in fetal malformations. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Avoid herbs and supplements with anticoagulant/antiplatelet activity. Examples include garlic, ginger, bilberry, danshen, piracetam, and ginkgo biloba.

Common Adverse effects

• Hemorrhage, Renal insufficiency, Dyspnea, Hypersensitivity reaction.

• Thienopyridines

If clopidogrel or prasugrel are administered during Cangrelor infusion, they will have no antiplatelet effect until the next dose is administered. Clopidogrel and prasugrel, therefore, should not be administered until Cangrelor infusion is discontinued.

The common side effects of Cangrelor include the following

Common

● Abdominal or stomach pain or swelling, back pain, black, tarry stools, blood in the eyes, blood in the urine, bruising or purple areas on the skin, coughing up blood, decreased alertness, dizziness, headache, joint pain or swelling, nosebleeds.

Rare

● Difficult or labored breathing, tightness in the chest, Cough, difficulty with swallowing, fast heartbeat, hives, itching, or rash, large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs, noisy breathing, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue, unusual tiredness or weakness.

• Pregnancy

Pregnancy Category

There are no available data on cangrelor use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Untreated myocardial infarction can be fatal to the pregnant women and fetus. In animal reproduction studies, continuous infusion of cangrelor in pregnant rats and rabbits throughout organogenesis at dose approximately 2-times the maximum recommended human dose (MRHD) did not result in fetal malformations. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

• Nursing Mothers

There are no data on the presence of Cangrelor in human milk or animal milk, the effects on the breastfed infant, or the effects on milk production. However, due to its short-half life, Cangrelor exposure is expected to be very low in the breastfed infant.

• Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

• Geriatric Use

In CHAMPION PHOENIX, 18% of patients were ≥75 years. No overall differences in safety or effectiveness were observed between these patients and those patients.

There is no specific treatment to reverse the antiplatelet effect of Cangrelor, but the effect is gone within one hour after the drug is discontinued. In clinical trials, 36 patients received an overdose of Cangrelor, ranging from 36 to 300 mcg/kg (bolus dose) or 4.8 to 13.7 mcg/kg/min (infusion dose). The maximum overdose received was 10 times the PCI bolus dose or 3.5 times the PCI infusion dose in 4 patients. No clinical sequela was noted as a result of overdose following completion of Cangrelor therapy.

Pharmacodynamic

Cangrelor inhibits activation and aggregation of platelets. After administration of a 30 mcg/kg IV bolus followed by a 4 mcg/kg/min IV infusion, platelet inhibition occurs within 2 minutes. Figure 2 shows the effect on platelet activity, and its relation to cangrelor plasma concentration, of administering a 30 mcg/kg IV bolus, followed by a 1-hour 4 mcg/kg/min IV infusion of cangrelor. The anti-platelet effect is maintained for the duration of the infusion. After discontinuation of the infusion, the anti-platelet effect decreases rapidly, and platelet function returns to normal within 1 hour.

Pharmacokinetics

• Absorption

Cangrelor is rapidly distributed and metabolized, reaching Cmax within 2 minutes after administration of an intravenous bolus followed by infusion.

• Distribution

In a study in healthy volunteers, Cangrelor administration at a dose of 30 mcg/kg bolus plus 4 mcg/kg/min showed a volume of distribution of 3.9 L. Plasma protein binding of Cangrelor is about 97-98%.

• Metabolism

Cangrelor is deactivated rapidly in the circulation by de-phosphorylation to its primary metabolite, a nucleoside, which has negligible anti-platelet activity. Cangrelor metabolism is independent of hepatic function, and it does not interfere with other drugs metabolized by hepatic enzymes.

• Excretion

Following IV administration of [3 H] Cangrelor 58% of radioactivity was recovered in urine. The remaining 35% of radioactivity was in feces, presumably following biliary excretion. The average elimination half-life of Cangrelor is about 3-6 minutes.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/204958s002lbl.pdf
• https://www.uptodate.com/contents/cangrelor-drug-information#F28640600
• https://www.mayoclinic.org/drugs-supplements/cangrelor-intravenous-route/side-effects/drg-20146785
• https://go.drugbank.com/drugs/DB06441
• https://reference.medscape.com/drug/kengreal-cangrelor-1000017#0
• https://www.rxlist.com/kengreal-drug.htm#indications