In clinical studies, healthy volunteers received up to two times the proposed daily dose. In clinical trials, the maximum accidental overdose was 10 times (bolus) or 3.5 times the infusion dose normally administered and bleeding was the most frequently observed adverse event.
Bleeding is the most likely pharmacological effect of overdose. If bleeding occurs appropriate supportive measures should be taken, which may include stopping the medicinal product so platelet function can return.
There is no antidote to Kengrexal, however, the pharmacokinetic half-life of Kengrexal is three to six minutes. Platelet function is restored within 60 minutes of stopping the infusion.
3 years.
The powder should be reconstituted immediately prior to dilution and use. Do not refrigerate.
From a microbiological point of view, unless the method of reconstitution/dilution precludes the risk of microbiological contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user.
- Active bleeding or increased risk of bleeding, because of impaired haemostasis and/or irreversible coagulation disorders or due to recent major surgery/trauma or uncontrolled severe hypertension.
- Any history of stroke or transient ischaemic attack (TIA).
-
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Mannitol
Sorbitol
Sodium hydroxide (for pH adjustment)
Powder for concentrate for solution for injection / infusion.
White to off-white lyophilised powder.
Summary of the safety profile
The safety of cangrelor has been evaluated in over 12,700 treated patients undergoing PCI. The most common adverse reactions with cangrelor include mild and moderate bleeding and dyspnoea. Serious adverse reactions associated with cangrelor in patients with coronary artery disease include severe/life threatening bleeding and hypersensitivity.
Tabulated list of adverse reactions
Table 1 depicts adverse reactions that have been identified based upon a pooling of combined data from all CHAMPION studies. Adverse reactions are classified according to frequency and System Organ Class. Frequency categories are defined according to the following conventions: Very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1,000 to <1/100), Rare (>1/10,000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).
Table 1: Adverse reactions for cangrelor in CHAMPION pooled studies within 48 hours
|
System organ class |
Common (>1/100 to <1/10) |
Uncommon (>1/1,000 to <1/100) |
Rare (>1/10,000 to <1/1,000) |
Very rare (<1/10,000) |
|
Infections and infestations |
Haematoma infection | |||
|
Neoplasms benign, malignant and unspecified (includes cysts and polyps) |
Skin neoplasm bleeding | |||
|
Blood and lymphatic system disorders |
Anaemia, Thrombo-cytopenia | |||
|
Immune system disorders |
Anaphylactic Reaction (Anaphylactic shock), Hypersensitivity | |||
|
Nervous system disorders |
Haemorrhage intracranial d * | |||
|
Eye disorders |
Eye haemorrhage | |||
|
Ear and labyrinth disorders |
Ear haemorrhage | |||
|
Cardiac disorders |
Cardiac tamponade (pericardial haemorrhage) | |||
|
Vascular disorders |
Haematoma <5 cm, Haemorrhage |
Haemodynamic instability |
Wound haemorrhage Vascular pseudoaneurysm | |
|
Respiratory, thoracic and mediastinal disorders |
Dyspnoea (Dyspnoea exertional) |
Epistaxis, Haemoptysis |
Pulmonary haemorrhage | |
|
Gastrointestinal disorders |
Retroperitoneal haemorrhage,* Peritoneal haematoma, Gastrointestinal haemorrhage a | |||
|
Skin and subcutaneous tissue disorders |
Ecchymosis (Petechiae, Purpura) |
Rash, Pruritus, Urticaria f |
Angioedema | |
|
Renal and urinary disorders |
Haemorrhage urinary tract, e Acute renal failure (renal failure) | |||
|
Reproductive system and breast disorders |
Pelvic haemorrhage |
Menorrhagia, Penile haemorrhage | ||
|
General disorders and administration site conditions |
Vessel puncture site discharge |
Vessel puncture site haematoma b | ||
|
Investigations |
Haematocrit decreased, Haemoglobin decreased** |
Blood creatinine increased |
Platelet count decreased, Red blood cell count decreased, International normalised ratio increased c | |
|
Injury, poisoning and procedural complications |
Haematoma >5 cm |
Contusion |
Periorbital haematoma, Subcutaneous haematoma |
Multiple related adverse reaction terms have been grouped together in the table and include medical terms as described below:
a. Upper gastrointestinal haemorrhage, Mouth haemorrhage, Gingival bleeding, Oesophageal haemorrhage, Duodenal ulcer haemorrhage, Haematemesis, Lower gastrointestinal haemorrhage, Rectal haemorrhage, Haemorrhoidal haemorrhage, Haematochezia
b. Application site bleeding, Catheter site haemorrhage or haematoma, Infusion site haemorrhage or haematoma
c. Coagulation time abnormal, Prothrombin time prolonged
d. Cerebral haemorrhage, Cerebrovascular accident
e. Haematuria, Blood urine present, Urethral haemorrhage
f. Erythema, Rash erythematous, Rash pruritic
* Including events with fatal outcome
** Transfusion was uncommon 101/12565 (0.8%)
Description of selected adverse reactions
The GUSTO bleeding scale was measured in the CHAMPION (PHOENIX, PLATFORM, and PCI) clinical trials. An analysis of non-CABG-related bleeding is presented in Table 2.
When administered in the PCI setting, cangrelor was associated with a greater incidence of GUSTO mild bleeding compared with clopidogrel. Further analysis of GUSTO mild bleeding revealed that a large proportion of mild bleeding events were ecchymosis, oozing and <5 cm haematoma. Transfusion and GUSTO severe/life-threatening bleeding rates were similar. In the pooled safety population from the CHAMPION trials, the incidence of fatal bleeding within 30 days of dosing was low and similar in patients who received cangrelor compared to clopidogrel (8 [0.1%] vs. 9 [0.1%]).
No baseline demographic factor altered the relative risk of bleeding with cangrelor.
Table 2: Non-CABG-related bleeding
|
GUSTO bleeding, n (%) | ||
|
CHAMPION pooled |
Cangrelor (N=12565) |
Clopidogrel (N=12542) |
|
Any GUSTO bleeding |
2196 (17.5) |
1696 (13.5) |
|
Severe/life-threatening |
28 (0.2) |
23 (0.2) |
|
Moderate |
76 (0.6) |
56 (0.4) |
|
Mild a |
2109 (16.8) |
1627 (13.0) |
|
Mild w/o ecchymosis, oozing and haematoma <5 cm |
707 (5.6) |
515 (4.1) |
|
Patients with any transfusion |
90 (0.7) |
70 (0.6) |
|
CHAMPION PHOENIX |
Cangrelor (N=5529) |
Clopidogrel (N=5527) |
|
Any GUSTO bleeding |
178 (3.2) |
107 (1.9) |
|
Severe/life-threatening |
9 (0.2) |
6 (0.1) |
|
Moderate |
22 (0.4) |
13 (0.2) |
|
Mild b |
150 (2.7) |
88 (1.6) |
|
Mild w/o ecchymosis, oozing and haematoma <5 cm |
98 (1.8) |
51 (0.9) |
|
Patients with any transfusion |
25 (0.5) |
16 (0.3) |
CABG: Coronary Artery Bypass Graft Surgery; GUSTO: Global Use of Strategies to Open Coronary Arteries; w/o: without
a In the CHAMPION pooled analysis, GUSTO Mild was defined as other bleed not requiring blood transfusion or causing haemodynamic compromise
b In CHAMPION PHOENIX, GUSTO Mild was defined as other bleeding requiring intervention but not requiring blood transfusion or causing haemodynamic compromise
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:
UK: Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
ROI: HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: [email protected]
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.
Kengrexal, co-administered with acetylsalicylic acid (ASA), is indicated for the reduction of thrombotic cardiovascular events in adult patients with coronary artery disease undergoing percutaneous coronary intervention (PCI) who have not received an oral P2Y12 inhibitor prior to the PCI procedure and in whom oral therapy with P2Y12 inhibitors is not feasible or desirable.
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 P2Y12â„¢ 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=5472) to clopidogrel (n=5470), 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. GPIIb/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 N=5470 |
Clopidogrel N=5469 |
OR (95% CI) |
p-value |
|
Primary Endpoint Death/MI/IDR/ST a |
257 (4.7) |
322 (5.9) |
0.78 (0.66,0.93) |
0.005 |
|
Key Secondary Endpoint |
|
|
|
|
|
Stent thrombosis |
46 (0.8) |
74 (1.4) |
0.62 (0.43, 0.90) |
0.010 |
|
Death |
18 (0.3) |
18 (0.3) |
1.00 (0.52, 1.92) |
>0.999 |
|
MI |
207 (3.8) |
255 (4.7) |
0.80 (0.67, 0.97) |
0.022 |
|
IDR |
28 (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 N=5462 |
Clopidogrel N=5457 |
OR (95% CI) |
p-value a |
|
Primary Endpoint Death/MI/IDR/ST |
326 (6.0) |
380 (7.0) |
0.85 (0.73, 0.99) |
0.035 |
|
Key Secondary Endpoint |
|
|
|
|
|
Stent thrombosis |
71 (1.3) |
104 (1.9) |
0.68 (0.50, 0.92) |
0.012 |
|
Death |
60 (1.1) |
55 (1.0) |
1.09 (0.76, 1.58) |
0.643 |
|
MI |
225 (4.1) |
272 (5.0) |
0.82 (0.68, 0.98) |
0.030 |
|
IDR |
56 (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.
Absorption
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.
Distribution
Cangrelor has a volume of distribution of 3.9 L. Cangrelor is 97-98% plasma-protein bound.
Biotransformation
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.
Elimination
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.
Linearity/non-linearity
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.
02/09/2016
Kengrexal 50 mg powder for concentrate for solution for injection / infusion.
Chiesi Farmaceutici S.p.A.
Via Palermo 26/A
43122 Parma
Italy
This medicinal product does not require any special storage conditions.
Powder in 10 mL glass vials (Type 1) closed with a Flurotec coated butyl rubber stopper and sealed with crimped aluminium seal.
Kengrexal is available in packs of 10 vials.
EU/1/15/994/001
Pregnancy
There are no or limited amount of data from the use of Kengrexal in pregnant women. Studies in animals have shown reproductive toxicity.
Kengrexal should not be used during pregnancy.
Breast-feeding
It is not known whether Kengrexal is excreted in human milk. A risk to the suckling child cannot be excluded.
Fertility
No effect on female fertility parameters were observed in animal studies of Kengrexal. A reversible effect on fertility was observed in male rats treated with Kengrexal.
Each vial contains cangrelor tetrasodium corresponding to 50 mg cangrelor. After reconstitution 1 mL of concentrate contains 10 mg cangrelor. After dilution 1 mL of solution contains 200 micrograms cangrelor.
Excipients with known effect
Each vial contains 52.2 mg sorbitol
Risk of bleeding
Treatment with Kengrexal may increase the risk of bleeding.
Although most bleeding associated with the use of cangrelor occurs at the site of arterial puncture, haemorrhage can occur at any site. Any unexplained fall in blood pressure or haematocrit should lead to the serious consideration of a haemorrhagic event and the cessation of cangrelor administration. Cangrelor should be used with caution in patients with disease states associated with an increased bleeding risk. Cangrelor should be used with caution in patients taking medicines that may increase the risk of bleeding.
Cangrelor has a half-life of three to six minutes. Platelet function is restored within 60 minutes of stopping infusion.
Intracranial haemorrhage
Treatment with Kengrexal may increase the risk of intracranial haemorrhage. In pivotal studies conducted in patients undergoing PCI, there were more intracranial bleeds at 30 days with cangrelor (0.07%) than with clopidogrel (0.02%), of which 4 bleeds with cangrelor and 1 bleed with clopidogrel were fatal. Cangrelor is contraindicated in patients with any history of stroke/TIA,.
Cardiac tamponade
Treatment with Kengrexal may increase the risk of cardiac tamponade. In pivotal studies conducted in patients undergoing PCI, there were more cardiac tamponades at 30 days with cangrelor (0.12%) than with clopidogrel (0.02%),.
Effects on renal function
In pivotal studies conducted in patients undergoing PCI, events of acute renal failure (0.1%), renal failure (0.1%) and increased serum creatinine (0.2%) were reported to occur after administration of cangrelor in clinical trials. In patients with severe renal impairment (creatinine clearance 15-30 mL/min) a higher rate of worsening in renal function (3.2%) was reported in the cangrelor group compared to clopidogrel (1.4%). In addition, a higher rate of GUSTO moderate bleeding was reported in the cangrelor group (6.7%) compared to clopidogrel (1.4%). Cangrelor should be used with caution in these patients.
Hypersensitivity
Hypersensitivity reactions may occur after treatment with Kengrexal. A higher rate of serious cases of hypersensitivity were recorded with cangrelor (0.05%) than with control (0.007%). These included cases of anaphylactic reactions/shock and angioedema,.
Risk of dyspnoea
Treatment with Kengrexal may increase the risk of dyspnoea. In pivotal studies conducted in patients undergoing PCI dyspnoea (including exertional dyspnoea) occurred more commonly in patients treated with cangrelor (1.3%) than clopidogrel (0.4%). Most dyspnoea events were mild or moderate in severity and the median duration of dyspnoea was two hours in patients receiving cangrelor,.
Fructose intolerance
This medicinal product contains sorbitol. Patients with rare hereditary problems of fructose intolerance should not take this medicine.
Sodium
Kengrexal contains less than 1 mmol sodium (23 mg) per vial, (i.e. essentially “sodium-freeâ€).
Kengrexal has no influence on the ability to drive and use machines.
Kengrexal should be administered by a physician experienced in either acute coronary care or in coronary intervention procedures and is intended for specialised use in an acute and hospital setting.
Posology
The recommended dose of Kengrexal for patients undergoing PCI is a 30 micrograms/kg intravenous bolus followed immediately by 4 micrograms/kg/min intravenous infusion.
Patients should be transitioned to oral P2Y12 therapy for chronic treatment.
Use with other anticoagulant agents
In patients undergoing PCI, standard procedural adjunctive therapy should be implemented.
Elderly
No dose adjustment is needed in elderly (>75 years) patients.
Renal impairment
No dose adjustment is needed in patients with mild, moderate or severe renal insufficiency.
Hepatic impairment
No dose adjustment is needed.
Paediatric population
The safety and efficacy of cangrelor in children aged less than 18 years has not been established. No data are available.
Method of administration
Kengrexal is intended for intravenous use, only after reconstitution and dilution.
Kengrexal should be administered via an intravenous line. The bolus volume should be administered rapidly (<1 minute), from the diluted bag via manual intravenous push or pump. Ensure the bolus is completely administered before the start of PCI. Start the infusion immediately after administration of the bolus.
Instructions for preparation
Aseptic procedures should be used for the preparation of Kengrexal.
The vial should be reconsituted immediately prior to dilution and use. To each 50 mg/vial, reconstitute by adding 5 mL of sterile water for injection. Swirl gently until all material is dissolved. Avoid vigorous mixing. Allow any foam to settle. Ensure that the contents of the vial are fully dissolved and the reconstituted material is a clear, colourless to pale yellow solution.
Do not use without dilution. Before administration, each reconstituted vial must be diluted further with 250 mL sodium chloride 9 mg/mL (0.9%) solution for injection or glucose (5%) solution for injection.
The medicinal product should be inspected visually for particulate matter after reconstitution.
Kengrexal is administered as a weight-based regimen consisting of an initial intravenous bolus followed by an intravenous infusion. The bolus and infusion should be administered from the infusion solution.
Withdraw 5 mL from one reconstituted vial and further dilute by adding to a 250 mL sodium chloride 9 mg/mL (0.9%) solution for injection or glucose (5%) solution for injection. Mix the bag thoroughly. This dilution will generate a concentration of 200 micrograms/mL and should be sufficient for at least two hours of dosing as required. Patients 100 kg and over will require a minimum of two bags.
Disposal
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Date of first authorisation: 23 March 2015
Interaction studies have only been performed in adults.
Oral P2Y12 agents (clopidogrel, prasugrel, ticagrelor)
When clopidogrel is administered during infusion of cangrelor, the expected inhibitory effect of clopidogrel on platelets is not achieved. Administration of 600 mg clopidogrel immediately after the cessation of the cangrelor infusion results in the anticipated full pharmacodynamic effect. No clinically relevant interruption of P2Y12 inhibition was observed in phase III studies when 600 mg clopidogrel was administered immediately after discontinuation of the cangrelor infusion.
A pharmacodynamic interaction study has been conducted with cangrelor and prasugrel, which demonstrated that cangrelor and prasugrel can be administered concomitantly. Patients can be transitioned from cangrelor to prasugrel when prasugrel is administered immediately following discontinuation of the cangrelor infusion or up to one hour before, optimally at 30 minutes before the end of the cangrelor infusion to limit recovery of platelet reactivity.
A pharmacodynamic interaction study has also been conducted with cangrelor and ticagrelor. No interaction on cangrelor was observed. Patients can be transitioned from cangrelor to ticagrelor without interruption of antiplatelet effect.
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 P2Y12â„¢ test, VASP-P and flow cytometry.
Following the administration of a 30 micrograms/kg bolus followed by a 4 micrograms/kg/min infusion (the PCI dose), 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, cangrelor blood levels decrease rapidly and platelet function returns to normal within one hour.
Acetylsalicylic acid (ASA), Heparin, Nitrogycerin
No pharmacokinetic or pharmacodynamic interaction with cangrelor was observed in an interaction study with aspirin, heparin, or nitroglycerin.
Bivalirudin, low molecular weight heparin, fondaparinux, and GP IIb/IIIa inhibitors
In clinical studies, cangrelor has been co-administered with bivalirudin, low molecular weight heparin, fondaparinux, and GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) with no apparent effect upon the pharmacokinetics or pharmacodynamics of cangrelor.
Cytochrome P450 (CYP)
Metabolism of cangrelor is not dependent on CYPs and CYP isoenzymes are not inhibited by therapeutic concentrations of cangrelor or its major metabolites.
Breast cancer resistance protein (BCRP)
In vitro inhibition of BCRP by the metabolite ARC-69712XX at clinically relevant concentrations has been observed. Possible implications for the in vivo situation have not been investigated, but caution is advised when cangrelor is to be combined with a BCRP substrate.
