Kengreal

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Kengreal

Classes

ADP (adenosine Diphosphate) Receptor Antagonist Platelet Aggregation Inhibitors

Administration
Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration.
Cangrelor is for intravenous use only.

Intravenous Administration

Reconstitution:
Reconstitute by adding 5 mL Sterile Water for Injection to a 50 mg cangrelor vial. Swirl gently until all material is dissolved. Do not mix vigorously. Allow foam to settle.
Ensure contents of the vial are fully dissolved. Reconstituted solution should be clear and colorless or pale yellow.
Withdraw contents of one reconstituted 50 mg vial and add to one 250 mL bag of 0.9% Sodium Chloride Injection or Dextrose 5% Injection resulting in a final infusion concentration of 200 mcg/mL.
One bag should be sufficient for most patients for at least 2 hours of dosing. Patients weighing more than 100 kg will require a minimum of 2 bags.
Administer diluted cangrelor immediately. When stored at room temperature, diluted cangrelor is stable for up to 12 hours in Dextrose 5% Injection and 24 hours in 0.9% Sodium Chloride Injection.
 
Intravenous Administration:
Administer cangrelor via a dedicated IV line.
Bolus injection should be administered rapidly (< 1 minute). The bolus volume may be withdrawn from the diluted infusion bag and administered via manual IV push or may be administered via infusion pump.
Ensure the bolus dose is completely administered prior to start of percutaneous coronary intervention (PCI).
Start the continuous IV infusion immediately after administration of the bolus; an infusion pump should be used for the continuous IV infusion.

Adverse Reactions
Severe

bleeding / Early / 0.2-0.2
intracranial bleeding / Delayed / 0.2-0.2
GI bleeding / Delayed / Incidence not known
retroperitoneal bleeding / Delayed / Incidence not known
bronchospasm / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
anaphylactic shock / Rapid / Incidence not known

Moderate

dyspnea / Early / 1.3-1.3
hematuria / Delayed / Incidence not known
hematoma / Early / Incidence not known
wheezing / Rapid / Incidence not known

Mild

ecchymosis / Delayed / Incidence not known

Common Brand Names

Kengreal

Dea Class

Rx

Description

Injectable P2Y12 platelet inhibitor indicated as an adjunct to PCI in patients not already receiving an oral P2Y12 inhibitor or glycoprotein IIb/IIIa inhibitor
Onset of platelet inhibitor occurs within 2 minutes of initiation of therapy and returns to normal within 1 hour of discontinuation
Contraindicated in patients with active significant bleeding

Dosage And Indications
For percutaneous coronary intervention (PCI) as an adjunct to reduce the risk of periprocedural myocardial infarction (i.e., myocardial infarction prophylaxis), repeat coronary revascularization, and stent thrombosis in persons who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor. Intravenous dosage Adults

30 mcg/kg IV bolus before PCI, followed 4 mcg/kg/minute continuous IV infusion for at least 2 hours or the duration of PCI, whichever is longer. Transition to an oral P2Y12 platelet inhibitor after cangrelor discontinuation to maintain platelet inhibition.

Dosing Considerations
Hepatic Impairment

Because the metabolism of cangrelor is not dependent on hepatic function, no dosage adjustment is required for patients with hepatic impairment.

Renal Impairment

No dosage adjustment is required for patients with mild, moderate, or severe renal impairment.

Drug Interactions

Abrocitinib: (Contraindicated) Concurrent use with cangrelor is contraindicated during the first 3 months of abrocitinib therapy due to an increased risk of bleeding with thrombocytopenia.
Caplacizumab: (Major) Avoid concomitant use of caplacizumab and cangrelor when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Clopidogrel: (Major) Do not administer clopidogrel until the cangrelor infusion is discontinued. The expected antiplatelet effect of a 600 mg loading dose of clopidogrel will be blocked if administered during the cangrelor infusion. Clopidogrel therapy should be initiated immediately after cangrelor discontinuation.
Defibrotide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like cangrelor is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue antithrombotic agents prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Prasugrel: (Major) Do not administer prasugrel until the cangrelor infusion is discontinued. The expected antiplatelet effect of a 60 mg loading dose of prasugrel will be blocked if administered during the cangrelor infusion. Prasugrel therapy should be initiated immediately after cangrelor discontinuation.
Selective serotonin reuptake inhibitors: (Moderate) Platelet aggregation may be impaired by selective serotonin reuptake inhibitors (SSRIs) due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymosis, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving platelet inhibitors (e.g., cangrelor). Patients should be instructed to monitor for signs and symptoms of bleeding while taking an SSRI concurrently with an antiplatelet medication and to promptly report any bleeding events to the practitioner.

How Supplied

Cangrelor/Kengreal Intravenous Inj Pwd F/Sol: 50mg

Maximum Dosage
Adults

30 mcg/kg IV bolus; 4 mcg/kg/minute IV infusion.

Geriatric

30 mcg/kg IV bolus; 4 mcg/kg/minute IV infusion.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Not indicated.

Neonates

Not indicated.

Mechanism Of Action

Cangrelor is a direct competitive inhibitor of the P2Y12 platelet receptor. Inhibition of the PY12 receptor prevents further signaling and platelet activation and thus results in inhibition of platelet activation and aggregation. In contrast to clopidogrel or prasugrel, cangrelor does not require hepatic conversion to an active metabolite.

Pharmacokinetics

Cangrelor is administered intravenously. Cangrelor is approximately 97% protein bound and undergoes rapid deactivation in the circulation by dephosphorylation to its inactive metabolite. Hepatic enzymes are not involved in the metabolism of cangrelor. The majority of cangrelor is excreted in urine. The average terminal half-life is 3—6 minutes.
 
Platelet inhibition occurs within 2 minutes after administration of a cangrelor 30 mcg/kg IV bolus followed by a 4 mcg/kg/minute IV infusion. Platelet inhibition is maintained throughout the duration of the infusion. After discontinuation of the cangrelor infusion, the anti-platelet effect decreases rapidly and platelet function returns to normal within 1 hour.

Intravenous Route

Cangrelor follows linear pharmacokinetics. It is rapidly distributed and metabolized. The maximum plasma concentration is achieved within 2 minutes after administration of an intravenous (IV) bolus followed by IV infusion.

Pregnancy And Lactation
Pregnancy

There are no available data on cangrelor use in human pregnancy to assess for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal reproduction studies, continuous infusion of cangrelor throughout organogenesis at a dose approximately 2 times the maximum recommended human dose (MRHD) did not result in any fetal malformations. In rat studies, dose-related fetal growth retardation, characterized by increased incidences of incomplete ossification and unossified hind limb metatarsals, was observed at doses of 3 mcg/kg/minute or more. In rabbit studies, increased abortion and intrauterine loss were observed at doses of 12 mcg/kg/minute or more (3 times the MRHD). Fetal growth retardation, characterized by decreased fetal weights, slight reduction in ossification, and a slight increase in skeletal variants, was observed at 36 mcg/kg/minute (9 times the MRHD). Cangrelor did not produce malformations in embryofetal development studies and is not considered to be a teratogen. Cangrelor use during labor and obstetric delivery may increase the risk for maternal bleeding and hemorrhage. Performance of neuraxial blockade procedures is not recommended during cangrelor use due to the potential risk of spinal hematoma. When possible, discontinue use of cangrelor 1 hour prior to labor, delivery, or neuraxial blockade. Myocardial infarction is a medical emergency, which can be fatal to the pregnant woman and the fetus if left untreated. Do not withhold life-sustaining therapy due to the potential concerns about the effect of cangrelor on the fetus.[59845]