Kengreal

An IV P2Y₁₂ receptor inhibitor
well suited for a wide range of PCI patients

KENGREAL reversibly binds to the adenosine diphosphate (ADP) P2Y₁₂ receptor.¹

Pharmacology

Rapid platelet inhibition for when you need it most

KENGREAL^® (cangrelor) is the first and only intravenous P2Y₁₂ receptor inhibitor¹:

Onset within

2 MINUTES

Offset within

1 HOUR

after discontinuation

KENGREAL reversibly binds to the ADP P2Y₁₂ receptor and is quickly eliminated once the infusion is stopped¹

Pharmacology¹

>98% inhibition of platelet aggregation in whole blood impedance aggregometry²

Phase I study in healthy volunteers (n=9); dose: 30 µg/kg IV bolus + 4 µg/kg/min IV infusion. Blood levels of cangrelor (green line/PK) and platelet activity (purple line/PD) were assessed over 150 minutes by whole blood impedance aggregometry in response to 20 µM of ADP.³

Infusion should be continued for at least 2 hours or for the duration of the procedure, whichever is longer¹

KENGREAL does not require a several-day washout period¹

Because of its offset within 1 hour, patients who need CABG or a valve replacement after PCI may proceed to surgery soon after KENGREAL discontinuation.

Efficacy and Safety

22% relative risk reduction in periprocedural thrombotic events^1,4

As an adjunct to PCI, KENGREAL^® (cangrelor) significantly reduced the primary composite endpoint of death, myocardial infarction (MI), ischemia-driven revascularization (IDR), and stent thrombosis (ST) events at 48 hours.^1,4

CHAMPION PHOENIX primary composite endpoint (death/MI/IDR/ST at 48 hours):
KENGREAL vs clopidogrel in an all-comer PCI patient population^1,4

Patients at risk

0 hr

6 hr

12 hr

18 hr

24 hr

30 hr

36 hr

42 hr

48 hr

KENGREAL

5472

5233

5229

5225

5223

5221

5220

5217

5213

Clopidogrel

5470

5162

5159

5155

5152

5151

5147

CHAMPION PHOENIX was a randomized, double-blind, placebo controlled, phase III trial in 11,145 patients who were undergoing either urgent or elective PCI and were receiving guideline-recommended therapy. Patients received a bolus and infusion of cangrelor or a loading dose of 600 mg or 300 mg of clopidogrel.

Clinical bleeding results⁴

Patients receiving KENGREAL had no statistically significant increase in either GUSTO-defined severe bleeding or need for transfusion.

Patient Profiles

Two potential patients in whom KENGREAL^® (cangrelor) may be appropriate

Kenneth^*

ACS, STEMI

66-year-old Caucasian male, retired construction worker

Symptoms:
- Developed chest tightness radiating to left arm while shoveling snow followed by nausea, vomiting, and diaphoresis
- Despite taking antacids, symptoms persisted for 2 hours
EMS administers aspirin, oxygen, and 2 mg IV morphine sulfate
Field ECG reveals 3 mm anterior ST-elevation

Action:
- Proceeded directly to cath lab for a PCI

Not an actual patient. Patient symptoms will vary; individual clinical evaluation should be done
to determine best course of therapy.

Medical History/ Social History

Hypertension, hyperlipidemia, GERD, peptic ulcer, type 2 diabetes mellitus
Smokes ½ pack of cigarettes per day, drinks 6 beers per week

Home Medications

Simvastatin 40 mg daily
Lisinopril 10 mg daily
Hydrochlorothiazide 25 mg daily
Omeprazole 40 mg daily
Janumet XR 50/1000 mg daily

Examinations/Labs

Height 177 cm, weight 97.7 kg, BMI 31
Pulse 110 bpm, BP 95/60 mmHg, respiratory rate 18 breaths per minute; rales are present bilaterally
Glucose 154 mg/dL

Cardiac Imaging

Proximal LAD occlusion at the origin of the first diagonal branch
LCX with a focal 70% stenosis in a medium-sized OM2
Dominant RCA with 80% mid-RCA stenosis, 60% PDA stenosis
LVEF 35% with moderate anterior and apical akinesis

Rafael^*

High-risk, Ad Hoc PCI

65-year-old Hispanic male, retired mechanic

History:
- STEMI 2 years ago with occlusion of OM1 treated with a 3.0 x 12-mm bare-metal stent
- Lost to follow-up

Symptoms:
- Presents to urgent care with exertional chest discomfort for past 2–3 months, controlled by sublingual nitroglycerin
- Denies rest symptoms

Tests:
- Nuclear stress test reveals lateral fixed defect with peri-infarct reversible ischemia

Action:
- Scheduled for outpatient cardiac catheterization

Not an actual patient. Patient symptoms will vary; individual clinical evaluation should be done
to determine best course of therapy.

Medical History/ Social History

Hypertension, osteoarthritis, peripheral vascular disease, lumbar laminectomy, depression
Smokes 1 pack of cigarettes per day, drinks 3 beers per day
On disability coverage due to his back injury

Home Medications

Aspirin 325 mg daily
Ibuprofen 800 mg 3–4 times daily
Bupropion SR 150 mg twice daily
Enalapril 5 mg daily
Sublingual nitroglycerin 0.4 mg prn

Examinations/Labs

Height 170 cm, weight 90.7 kg, BMI 31
Pulse 74 bpm, BP 124/84 mmHg, respiratory rate 16 breaths per minute
Total cholesterol 224 mg/dL

Cardiac Imaging

70% restenosis of OM1

Dosing Considerations¹

Adjust KENGREAL^® (cangrelor) dose based on patient weight to meet the recommended 30 µg/kg IV bolus and 4 µg/kg/min IV infusion
- Remove the bolus from the IV bag, never from the reconstituted vial
The maintenance infusion should be continued for at least 2 hours or for the duration of the PCI, whichever is longer
Dose adjustment is not required in elderly patients (≥75 years) or in patients with renal or hepatic insufficiency
To maintain platelet inhibition after discontinuation of KENGREAL infusion, an oral P2Y₁₂ platelet inhibitor should be administered
- Ticagrelor: 180 mg at any time during KENGREAL infusion or immediately after discontinuation
- Prasugrel: 60 mg immediately after KENGREAL discontinuation^†
- Clopidogrel: 600 mg immediately after KENGREAL discontinuation^†

†

If clopidogrel or prasugrel is administered during KENGREAL infusion, it will have no antiplatelet effect until the next dose is administered.

Reimbursement

For Medicare, when used as part of a hospital outpatient PCI procedure, reimbursement for KENGREAL^® will be separate from the Comprehensive APC payment received for the outpatient PCI procedure. Medicare usually prefers and some private payers and Medicaid accept C-codes in the outpatient setting.

View the Reimbursement Guide Executive Summary for more information.

COMPANY:

Chiesi USA, Inc.

PHARMACOLOGIC CLASS:

P2Y₁₂ platelet inhibitor (ATP analog).

INGREDIENTS:

Cangrelor for Injection is a sterile white to off-white lyophilized powder for IV infusion. In addition to the active ingredient, cangrelor, each single-use vial contains mannitol, sorbitol, and sodium hydroxide to adjust the pH.

INDICATION:

As adjunct to PCI for reducing the risk of periprocedural MI, repeat coronary revascularization, and ST in patients who have not been treated with a P2Y₁₂ platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor.

ADULTS:

Administer 30 mcg/kg IV bolus prior to PCI, followed immediately by 4 mcg/kg/min IV infusion; continue infusion for ≥2 hours or for duration of PCI, whichever is longer.
To maintain platelet inhibition after discontinuation of KENGREAL infusion, an oral P2Y₁₂ platelet inhibitor should be administered: see full labeling.

PEDIATRIC USE:

Safety and effectiveness in pediatric patients have not been established.

CONTRAINDICATIONS:

Significant active bleeding.
Hypersensitivity to KENGREAL or any component of the product.

WARNINGS/ PRECAUTIONS:

Drugs that inhibit platelet P2Y₁₂ function, including KENGREAL, increase the risk of bleeding.

DRUG INTERACTIONS:

Clopidogrel: Do not administer until KENGREAL infusion is discontinued.
Prasugrel: Do not administer until KENGREAL infusion is discontinued.

ADVERSE REACTIONS:

The most common adverse reaction is bleeding.

HOW
SUPPLIED:

Sterile lyophilized powder in single-use 10 mL vial.

Important Safety Information

KENGREAL^® (cangrelor) for Injection is contraindicated in patients with significant active bleeding.

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

Drugs that inhibit platelet P2Y₁₂ function, including KENGREAL^®, increase the risk of bleeding. In CHAMPION PHOENIX, bleeding events of all severities were more common with KENGREAL^® than with clopidogrel. Bleeding complications with KENGREAL^® were consistent across a variety of clinically important subgroups. Once KENGREAL^® is discontinued, there is no antiplatelet effect after an hour.

The most common adverse reaction is bleeding.

Indication

KENGREAL^® (cangrelor) for Injection is a P2Y₁₂ platelet inhibitor 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.

Click here for Full Prescribing Information.

REFERENCES

KENGREAL [Prescribing Information]. Cary, NC: Chiesi USA, Inc.; 2016.
Data on file. Chiesi USA, Inc.
Akers WS, Oh JJ, Oestreich JH, et al. Pharmacokinetics and pharmacodynamics of a bolus and infusion of cangrelor: a direct, parenteral P2Y₁₂ receptor antagonist. J Clin Pharmacol. 2010;50(1):27-35.
Bhatt DL, Stone GW, Mahaffey KW, et al; CHAMPION PHOENIX Investigators. Effect of platelet inhibition with cangrelor during PCI on ischemic events. N Engl J Med. 2013;368(14):1303-1313.

This MPR Prescribing Alert is produced as a basic reminder of important information for healthcare professionals. Readers are advised to consult manufacturers and specialists if questions arise about specific products, treatments, or diseases. The publisher and editors do not assume liability for any errors or omissions. MPR and MPR Prescribing Alert are registered trademarks of Haymarket Media, Inc.

Pharmacology

Pharmacology1

KENGREAL does not require a several-day washout period1

Efficacy and Safety

CHAMPION PHOENIX primary composite endpoint (death/MI/IDR/ST at 48 hours): KENGREAL vs clopidogrel in an all-comer PCI patient population1,4

Clinical bleeding results4