Canegrelor- Kengreal -@- (June 2015)- Anti-coagulant
Drug Name:Canegrelor- Kengreal -@- (June 2015)- Anti-coagulant
List Of Brands:
Indication Type Description:
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Indication:
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use
KENGREAL safely and effectively. See full prescribing information for KENGREAL. KENGREAL™ (cangrelor) for injection, for intravenous use
Initial U.S. Approval: 2015
INDICATIONS AND USAGE
KENGREAL is a P2Y12 platelet inhibitor indicated as an adjunct to percutaneous coronary intervention (PCI) for reducing the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients in who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor
NEW MOLECULAR ENTITY AND NEW THERAPEUTIC BIOLOGICAL
PRODUCTS APPROVED FOR 2015
Certain drugs are classified as New molecular Emtities- NME- for FDA review
Many of these products contain active moieties that have not been approved
by FDA previously, either as a single ingredient or as part of a combination
products; these products frequently provide important new therapies for the
patients.
Some drugs are characterized as NMEs for administrative purposes ,but
nonetheless contain certain active moieties in products that have been
previously approved by FDA. For example, CDER classifies biological
products submitted in an application under section 351(a) of the Public
Service Act as NME for purposes of FDA review, regardless of whether
the agency previously approved a related active moiety in a different
product.
FDAs classification of a drug as an -NME- for review purposes is distinct
from FDAs determination of whether a drug is a - New Chemical Entity or - NCE-
within the meaning of the Federal Food,Drug, and Cosmetic Act
No.14
Drug Name - Canegrelor
Active Ingredient- Kengreal
Date of approval - 6/22/2015
FDA-approved use - To prevent formation of harmful blood clots
in coronary arteries for adult patients
undergoing percutaneous coronary intervention
Approved by US FDA on 6/22/2015- (Ref- FDA approved List- 2015)
Adverse Reaction:
ADVERSE REACTIONS
The most common adverse reaction is bleeding
Contra-Indications:
CONTRAINDICATIONS
Significant active bleeding
Hypersensitivity to KENGREAL or any component of the product (
WARNINGS AND PRECAUTIONS
Bleeding: Like other drugs that inhibit platelet P2Y12 function, KENGREAL can increase the risk of bleeding
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
KENGREAL is a P2Y12 platelet inhibitor indicated as an adjunct to percutaneous coronary intervention (PCI) for reducing the risk of periprocedural myocardial infarction (MI), repeat coronary revascularization, and stent thrombosis (ST) in patients in who have not been treated with a P2Y12 platelet inhibitor and are not being given a glycoprotein IIb/IIIa inhibitor
DOSAGE AND ADMINISTRATION
KENGREAL is intended for administration via a dedicated IV line, only after reconstitution and dilution. (
Administer 30 µg/kg intravenous (IV) bolus prior to PCI followed immediately by a 4 µg/kg/min IV infusion for at least 2 hours or duration of procedure, whichever is longer.
To maintain platelet inhibition after discontinuation of KENGREAL infusion, an oral P2Y12 platelet inhibitor should be administered.
DOSAGE FORMS AND STRENGTHS
Single-use 10 mL vial containing 50 mg KENGREAL as a lyophilized powder for reconstitution
Patient Information:
HOW SUPPLIED/STORAGE AND HANDLING
KENGREAL is supplied as a sterile lyophilized powder in single use 10 mL vials.
10 mL vial containing 50 mg cangrelor
10 count of 10 mL vials containing 50 mg cangrelor
Vials of KENGREAL should be stored at USP Controlled Room Temperature, [20°C to 25°C (68°F to 77°F) with excursions between 15°C and 30°C (59°F and 86°F) permitted].
Distributed by: The Medicines Company Parsippany, NJ 07054
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1.Mechanism of Action
Cangrelor is a direct P2Y12 platelet receptor inhibitor that blocks ADP-induced platelet activation and aggregation. Cangrelor binds selectively and reversibly to the P2Y12 receptor to prevent further signaling and platelet activation.
2.Pharmacodynamics
Cangrelor inhibits activation and aggregation of platelets. After administration of a 30 mcg/kg IV bolus followed by a 4 mcg/kg/min IV infusion, platelet inhibition occurs within 2 minutes.
The anti-platelet effect is maintained for the duration of the infusion. After discontinuation of the infusion, the anti-platelet effect decreases rapidly and platelet function returns to normal within 1 hour.
3.Pharmacokinetics
KENGREAL administered intravenously has linear pharmacokinetics in both healthy volunteers and patients. KENGREAL is rapidly distributed and metabolized, reaching Cmax within 2 minutes after administration of an intravenous bolus followed by infusion.
Distribution-
In a study in healthy volunteers, KENGREAL administration at a dose of 30 mcg/kg bolus plus 4 mcg/kg/min showed a volume of distribution of 3.9 L. Plasma protein binding of KENGREAL is about 97-98%.
Metabolism-
KENGREAL is deactivated rapidly in the circulation by dephosphorylation to its primary metabolite, a nucleoside, which has negligible anti-platelet activity. KENGREAL’s metabolism is independent of hepatic function and it does not interfere with other drugs metabolized by hepatic enzymes.
Elimination-
Following IV administration of [3H] KENGREAL 58% of radioactivity was recovered in urine. The remaining 35% of radioactivity was in feces, presumably following biliary excretion. The average elimination half-life of KENGREAL is about 3-6 minutes.
Specific Populations-
KENGREAL pharmacokinetics are not affected by sex, age, renal status or hepatic function. No dose adjustment is needed for these factors
Weight Although weight was a significant covariate for PK with higher clearance in heavier patients, the impact of weight on drug exposure is accounted by the use of weight-based dosing.
Drug-Drug Interactions
Co-administration of cangrelor with unfractionated heparin, aspirin, and nitroglycerin was formally studied in healthy subjects, with no evidence of an effect on the PK/PD of cangrelor.
In clinical trials cangrelor has been co-administered with bivalirudin, low molecular weight heparin, clopidogrel, prasugrel, and ticagrelor without clinically detectable interactions.
The expected antiplatelet effect of a 600 mg loading dose of clopidogrel or a 60 mg loading dose of prasugrel was blocked when clopidogrel or prasugrel was administered during a cangrelor infusion
In contrast, the antiplatelet effect of a 180 mg ticagrelor loading dose was not altered significantly when ticagrelor was administered during cangrelor infusion
Administering ticagrelor during cangrelor infusion does not attenuate the anti-platelet effect of ticagrelor. In vitro studies suggest that neither cangrelor nor its major metabolites inhibit the activity of the hepatic CYP isoenzymes at therapeutic concentrations.
Therefore, cangrelor administration is not expected to interfere with the hepatic metabolism of other concomitantly administered therapeutic agents. 10
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy-
Pregnancy Category C
There are no adequate and well-controlled studies of KENGREAL in pregnant women. Cangrelor did not produce malformations in either the rat or rabbit reproductive studies, and is not considered to be a teratogen.
2.Nursing Mothers
It is not known whether KENGREAL is excreted in human milk.
3.Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
4.Geriatric Use
In CHAMPION PHOENIX, 18% of patients were =75 years. No overall differences in safety or effectiveness were observed between these patients and those patients <75 years
5.Renal Impairment
No dosage adjustment is required for patients with mild, moderate, or severe renal impairment
6.Hepatic Impairment
KENGREAL has not been studied in patients with hepatic impairment. However, the metabolism of KENGREAL is not dependent of hepatic function, so that dosage adjustment is not required for patients with hepatic impairment
OVERDOSAGE
There is no specific treatment to reverse the antiplatelet effect of KENGREAL but the effect is gone within one hour after the drug is discontinued.
In clinical trials, 36 patients received an overdose of KENGREAL, ranging from 36 to 300 mcg/kg (bolus dose) or 4.8 to 13.7 mcg/kg/min (infusion dose).
The maximum overdose received was 10 times the PCI bolus dose or 3.5 times the PCI infusion dose in 4 patients. No clinical sequela were noted as a result of overdose following completion of KENGREAL therapy.
