Side Effects of Kengreal (cangrelor)

Kengreal (cangrelor) is a type of anti-platelet drug called a P2Y12 inhibitor used during percutaneous coronary intervention (PCI) to reduce the risk of heart attacks, repeat coronary revascularization, and stent thrombosis (ST) in patients who have not been treated with another P2Y12 platelet inhibitor and are not receiving a glycoprotein IIb/IIIa inhibitor, another class of platelet inhibitor. 

Kengreal prevents blood clots by reversibly binding to the P2Y12 receptor on platelets, preventing adenosine diphosphate (ADP) from activating platelets. It belongs to a class of drugs called P2Y12 inhibitors. 

Kengreal is different from other P2Y12 inhibitors because it prevents clotting faster and its effect does not last as long after it is stopped. After administration, platelet inhibition begins within 2 minutes, lasts for the duration of the infusion, and platelet function returns to normal within 1 hour after stopping the infusion.

Common side effects of Kengreal include

• bleeding and
• shortness of breath.

Serious side effects of Kengreal include

• severe bleeding,
• increased risk of kidney impairment, and
• allergic reactions, including
  • anaphylaxis.

Drug interactions of Kengreal include clopidogrel or prasugrel given during Kengreal infusion because they will have no antiplatelet effect until the next dose is given. Therefore, clopidogrel and prasugrel should not be given until the Kengreal infusion is stopped. 

Use of Kengreal in pregnant females has not been adequately studied. 

It is unknown if Kengreal is excreted in human milk. Consult your doctor before breastfeeding.

The most common adverse effect of cangrelor are:

• Bleeding
• Shortness of breath

Other side effects include:

• Increased risk of kidney impairment

Possible serious side effects include:

• Allergic reactions
• Severe bleeding
• Anaphylaxis

The following adverse reactions are also discussed elsewhere in the labeling:

• Bleeding

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of Kengreal has been evaluated in 13,301 subjects in controlled trials, in whom, 5,529 were in the Champion Phoenix trial.

Bleeding

There was a greater incidence of bleeding with Kengreal than with clopidogrel. No baseline demographic factor altered the relative risk of bleeding with Kengreal (see Table 1 and Figure 1).

Table 1: Major Bleeding Results in the Champion Phoenix Study (Non-CABG related Bleeding)^a

Figure 1: Bleeding Results in the Champion Phoenix Study^a (All Non-CABG related)

Bleeding Results in the Champion Phoenix Study - Illustration

^a Safety population is all randomized subjects who received at least one dose of study drug Note: The figure above presents effects in various subgroups most of which are baseline characteristics and most of which were pre-specified (patient presentation and weight were not pre-specified subgroups). The 95% confidence limits that are shown do not take into account how many comparisons were made, nor do they reflect the effect of a particular factor after adjustment for all other factors. Apparent homogeneity or heterogeneity among groups should not be over-interpreted.

Drug Discontinuation

• In Champion Phoenix the rate of discontinuation for bleeding events was 0.3% for Kengreal and 0.1% for clopidogrel.
• Discontinuation for non-bleeding adverse events was low and similar for Kengreal (0.6%) and for clopidogrel (0.4%).
• Coronary artery dissection, coronary artery perforation, and dyspnea were the most frequent events leading to discontinuation in patients treated with Kengreal.

Non-Bleeding Adverse Reactions

Hypersensitivity

• Serious cases of hypersensitivity were more frequent with Kengreal (7/13301) than with control (2/12861).
• These included
  • anaphylactic reactions,
  • anaphylactic shock,
  • bronchospasm,
  • angioedema, and
  • stridor.

Decreased renal function

• Worsening renal function was reported in 3.2% of Kengreal patients with severe renal impairment (creatinine clearance < 30 mL/min) compared to 1.4% of clopidogrel patients with severe renal impairment.

Dyspnea

• Dyspnea was reported more frequently in patients treated with Kengreal (1.3%) than with control (0.4%).

Thienopyridines

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