KENGREXAL Powder for concentrate solution

Active ingredients: Cangrelor

Pharmacodynamic properties

Pharmacotherapeutic group: Platelet aggregation inhibitors excluding heparin
ATC code: B01AC25

Mechanism of action

Kengrexal contains cangrelor, a direct P2Y12 platelet receptor antagonist that blocks adenosine diphosphate (ADP)-induced platelet activation and aggregation in vitro and ex vivo. Cangrelor binds selectively and reversibly to the P2Y12 receptor to prevent further signalling and platelet activation.

Pharmacodynamic effects

Cangrelor exhibits inhibition of activation and aggregation of platelets as shown by aggregometry (light transmission and impedance), point-of care assays, such as the VerifyNow P2Y12 test, VASP-P and flow cytometry. Onset of P2Y12 inhibition occurs rapidly upon cangrelor administration.

Following the administration of a 30 microgram/kg bolus followed by a 4 microgram/kg/min infusion, platelet inhibition is observed within two minutes. The pharmacokinetic/pharmacodynamic (PK/PD) effect of cangrelor is maintained consistently for the duration of the infusion.

Irrespective of dose, following cessation of the infusion, blood levels decrease rapidly and platelet function returns to normal within one hour.

Clinical efficacy and safety

The primary clinical evidence for the efficacy of cangrelor is derived from CHAMPION PHOENIX, a randomised, double-blind study comparing cangrelor (n=5,472) to clopidogrel (n=5,470), both given in combination with aspirin and other standard therapy, including unfractionated heparin (78%), bivalirudin (23%), LMWH (14%) or fondaparinux (2.7%). The median duration of cangrelor infusion was 129 minutes. GP IIb/IIIa inhibitors were permitted for bailout use only and were used in 2.9% of patients. Patients with coronary atherosclerosis were included who required PCI for stable angina (58%), non-ST-segment elevation acute coronary syndrome (NSTE-ACS) (26%), or ST-elevation myocardial infraction (STEMI) (16%).

Data from the CHAMPION pooled population of over 25,000 PCI patients provide additional clinical support for safety.

In CHAMPION PHOENIX, cangrelor significantly reduced (relative risk reduction 22%; absolute risk reduction 1.2%) the primary composite endpoint of all-cause mortality, MI, IDR, and ST compared to clopidogrel at 48 hours (Table 3).

Table 3. Thrombotic events at 48 hours in CHAMPION PHOENIX (mITT population):

  Cangrelor vs. Clopidogrel
n (%)Cangrelor Ν=5470Clopidogrel Ν=5469OR (95% CI)p-value
Primary Endpoint
Death/MI/IDR/STa257 (4.7)322 (5.9)0.78 (0.66. 0.93)0.005
Key Secondary Endpoint
Stent thrombosis46 (0.8)74 (1.4)0.62 (0.43. 0.90)0.010
Death18 (0.3)18 (0.3)1.00 (0.52. 1.92)>0.999
MI207 (3.8)255 (4.7)0.80 (0.67. 0.97)0.022
IDR28 (0.5)38 (0.7)0.74 (0.45. 1.20)0.217

a Primary endpoint from logistic regression adjusted for loading dose and patient status. p-values for secondary endpoints based on Chi-squared test.
OR = odds ratio; CI = confidence interval; IDR = ischaemia-driven revascularisation; MI = myocardial infarction; mITT = modified intent-to-treat; ST = stent thrombosis.

Significant reductions in death/MI/IDR/ST and ST observed in the cangrelor group at 48 hours were maintained at 30 days (Table 4).

Table 4. Thrombotic events at 30 days in CHAMPION PHOENIX (mITT population):

  Cangrelor vs. Clopidogrel
n (%)Cangrelor Ν=5462Clopidogrel Ν=5457OR (95% CI)p-valuea
Primary Endpoint
Death/MI/IDR/ST326 (6.0)380 (7.0)0.85 (0.73. 0.99)0.035
Key Secondary Endpoint
Stent thrombosis71 (1.3)104 (1.9)0.68 (0.50. 0.92)0.012
Death60 (1.1)55 (1.0)1.09 (0.76. 1.58)0.643
MI225 (4.1)272 (5.0)0.82 (0.68. 0.98)0.030
IDR56 (1.0)66 (1.2)0.85 (0.59. 1.21)0.360

a p-values based on Chi-squared test.
OR = odds ratio; CI = confidence interval; IDR = ischaemia-driven revascularisation; MI = myocardial infarction; mITT = modified intent-to-treat; ST = stent thrombosis.

Paediatric Population

The European Medicines Agency has deferred the obligation to submit the results of studies with Kengrexal in one or more subsets of the paediatric population in the prevention of non-site specific embolism and thrombosis, for the treatment of thrombosis in paediatric patients undergoing diagnostic and/or therapeutic percutaneous vascular procedures. See section 4.2 for information on paediatric use.

Pharmacokinetic properties


The bioavailability of cangrelor is complete and immediate. Cangrelor is rapidly distributed reaching Cmax within two minutes after administration of an intravenous bolus followed by infusion. The mean steady state concentration of cangrelor during a constant intravenous infusion of 4 micrograms/kg/min is 488 ng/mL.


Cangrelor has a volume of distribution of 3.9 L. Cangrelor is 97-98% plasma-protein bound.


Cangrelor is deactivated rapidly in the plasma by dephosphorylation to form its primary metabolite, a nucleoside. The metabolism of cangrelor is independent of organ function and does not interfere with other drugs metabolised by hepatic enzymes.


The half-life of Kengrexal is three to six minutes, independent of dose. Following the intravenous administration of a 2 micrograms/kg/min infusion of [3H] cangrelor to healthy male volunteers, 93% of total radioactivity was recovered. Of the recovered material, 58% was found in urine and the remaining 35% was found in faeces, presumably following biliary excretion. Initial excretion was rapid, such that approximately 50% of the administered radioactivity was recovered in the first 24 hours, and 75% was recovered by 48 hours. Mean clearance was approximately 43.2 L/kg.


The pharmacokinetic properties of cangrelor have been evaluated and found to be linear in patients and healthy volunteers.

Pharmacokinetic/pharmacodynamic relationship(s)

Special populations

The pharmacokinetics of cangrelor are not affected by gender, age, or renal or hepatic status. No dose adjustment is needed for these populations.

Paediatric population

Cangrelor has not been evaluated in a paediatric population (see sections 4.2 and 5.1).

Preclinical safety data

Non-clinical data reveal no special safety risk for humans based on studies of safety pharmacology, mutagenicity and clastogenic potential.

Carcinogenicity studies have not been performed.

The primary adverse effects of cangrelor in rats and dogs occurred in the upper urinary tract and consisted of injury to renal tubules, renal pelvis, and ureter. Anatomical changes correlated with increased plasma creatinine and urea, and increased albumin and blood cells in urine. Injury to the urinary tract was reversible following cessation of dosing in an investigative study in rats.

Reproductive toxicity

Cangrelor produced dose-related foetal growth retardation characterised by increased incidences of incomplete ossification and unossified hind limb metatarsals in rats. In rabbits, cangrelor was associated with increased incidences of abortion and intrauterine losses, as well as foetal growth retardation at higher doses which may have been secondary to maternal toxicity. Cangrelor did not produce malformations in either the rat or rabbit reproductive studies.

Impairment of fertility

Effects on fertility, ability to produce a pregnancy with female partner(s), sperm morphology and sperm motility were observed in the male rat fertility study when cangrelor was administered at human equivalent doses equal to 1.8 fold the recommended PCI dose. These effects were not apparent at lower doses and were reversible following cessation of dosing. In this study, semen analysis was conducted after 8 weeks of continuous treatment.

Female fertility was not affected at any dose.