Cangrelor

Cangrelor is an intravenous, reversible P2Y12 receptor antagonist with a very short half life. It gives immediate platelet inhibition during percutaneous coronary intervention in patients who have not received an oral P2Y12 inhibitor and cannot take one by mouth. Platelet function returns to normal within an hour of stopping. It is not available in most East African hospitals.

Classification. Antiplatelet; intravenous ATP analogue P2Y12 inhibitor (reversible).

Mechanism. Binds the platelet P2Y12 receptor reversibly and blocks ADP induced activation and aggregation.

Pharmacodynamics. Onset within 2 minutes; steady state in 30 minutes. Offset within 60 minutes of stopping.

Pharmacokinetics. Half life 3 to 6 minutes. Broken down in the plasma by dephosphorylation to an inactive metabolite, independent of liver or kidney function. Excreted in urine (58%) and faeces (35%).

Percutaneous coronary intervention in patients not pre treated with an oral P2Y12 inhibitor, adult.

• Bolus 30 micrograms/kg IV before the procedure.

• Infusion 4 micrograms/kg/minute started with the bolus, continued for at least 2 hours or for the duration of the procedure, whichever is longer (up to 4 hours).

• Transition to oral therapy: ticagrelor 180 mg during the infusion or at its end; prasugrel 60 mg at the end of the infusion; clopidogrel 600 mg at the end of the infusion (not during it).

Children. Not established.

Contraindications. Active bleeding; history of stroke or transient ischaemic attack in some labels; hypersensitivity.

Warnings. Bleeding; dyspnoea; transient kidney function change; give clopidogrel only after the infusion has finished because cangrelor blocks the binding of the clopidogrel active metabolite.

Adverse effects. Bleeding, bruising, dyspnoea, access site haematoma, transient creatinine rise, rarely hypersensitivity.

Interactions. Clopidogrel (given during the infusion): blocked effect. Anticoagulants, aspirin, other antiplatelet drugs: bleeding. Prasugrel and ticagrelor: no interaction when given as directed.

Special groups.

• Pregnancy: avoid; no data.

• Breastfeeding: no data; avoid.

• Patients of African ancestry: no dose change.

• Older adults: no adjustment; bleeding vigilance.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment.

Formulations. Powder for infusion 50 mg vial.

Administration. Reconstitute with 5 mL of water for injection and dilute in 250 mL of 0.9% sodium chloride or 5% glucose; give the bolus quickly and infuse by pump in a dedicated line.

Baseline. Haemoglobin, platelet count, creatinine, history of bleeding or stroke.

Monitoring. Access site and bleeding; haemoglobin after the procedure; dyspnoea.

Stopping. Stop the infusion at the end of the procedure or after 2 to 4 hours; platelet function normalises within 1 hour.

Common prescribing errors. Giving clopidogrel during the infusion; failing to start an oral P2Y12 inhibitor at the end of the infusion; using it in patients already loaded with oral P2Y12 inhibitors; infusing for less than 2 hours when a long procedure or high risk is expected.