Sandbox Ticagrelor

Sandbox Ticagrelor®
Black Box Warning
Adult Indications and Dosage
Pediatric Indications and Dosage
Contraindications
Warnings
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration and Monitoring
IV Compatibility
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient information
Precautions with Alcohol
Brand Names
Look-Alike Drug Names
Drug Shortage Status
Price

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Sheng Shi, M.D. [2]

For information about (Generic Name), click here.

Synonyms / Brand Names: Brilinta

Disclaimer

WikiDoc Drug Project is a constellation of drug information for healthcare providers and patients vigorously vetted on the basis of FDA package insert, MedlinePlus, Practice Guidelines, Scientific Statements, and scholarly medical literature. The information provided is not a medical advice or treatment. WikiDoc does not promote any medication or off-label use of drugs. Please read our full disclaimer here.

Black Box Warning

FDA Package Insert for Sandbox Ticagrelor contains no information regarding Black Box Warning.

WARNING: (A) BLEEDING RISK, and (B) ASPIRIN DOSE AND Brilinta EFFECTIVENESS See full prescribing information for complete boxed warning. Condition Name: Brilinta, like other antiplatelet agents, can cause significant, sometimes fatal bleeding. Do not use Brilinta in patients with active pathological bleeding or a history of intracranial hemorrhage. Do not start Brilinta in patients planned to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue Brilinta at least 5 days prior to any surgery. Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgery. If possible, manage bleeding without discontinuing Brilinta. Stopping Brilinta increases the risk of subsequent cardiovascular events.

Overview

Sandbox Ticagrelor is a ADP-induced aggregation inhibitor, platelet aggregation inhibitor that is FDA approved for the treatment of acute coronary syndromes, There is a Black Box Warning for this drug as shown here. Common adverse reactions include bleeding, major and minor, headache, serum creatinine raised, cough, dyspnea.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Acute coronary syndromes

• Dosing Information

• Initial dose: “Brilinta 180 mg PO once” with aspirin (325 mg) once.
• Maintenance dose: “Brilinta 90 mg PO bid” with aspirin 75-100 mg PO qd.

• Not recommended when aspirin maintenance dose is above 100 mg.

Percutaneous coronary intervention

• Dosing Information

• Loading dose: “Brilinta 180 mg PO” with aspirin (325 mg), once.
• Maintenance: “Brilinta 90 mg PO bid” with aspirin 75-100 mg qd.

• Use of aspirin maintenance dose above 100 mg is not recommended.
• Consider carefully the continuation of therapy beyond 12 months (for drug-eluting stents).

Off-Label Use and Dosage (Adult)

There is limited information about Off-Label Use and Dosage of Ticagrelor tablet in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information about FDA-Labeled Indications and Dosageof Ticagrelor tablet in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information about Off-Label Use and Dosage of Ticagrelor tablet in pediatric patients.

Contraindications

• History of intracranial hemorrhage
• Active pathological bleeding
• Severe hepatic impairment
• Hypersensitivity to ticagrelor or any component of the product

Warnings

• Like other antiplatelet agents, Brilinta increases the risk of bleeding.
• In PLATO, use of Brilinta with maintenance doses of aspirin above 100 mg decreased the effectiveness of Brilinta.
• Moderate Hepatic Impairment: Consider the risks and benefits of treatment, noting the probable increase in exposure to ticagrelor.
• Dyspnea: Dyspnea was reported more frequently with Brilinta than with clopidogrel. Dyspnea resulting from Brilinta is self-limiting. Rule out other causes.
• Discontinuation of Brilinta: Premature discontinuation increases the risk of myocardial infarction, stent thrombosis, and death.

(Description)

Adverse Reactions

Clinical Trials Experience

Clinical Trials Experience

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

Because clinical trials are conducted under widely varying conditions, adverse reaction 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.

Brilinta has been evaluated for safety in more than 10000 patients, including more than 3000 patients treated for more than 1 year.

_Bleeding

PLATO used the following bleeding severity categorization:

• Major bleed – fatal/life-threatening. Any one of the following: fatal; intracranial; intrapericardial bleed with cardiac tamponade; hypovolemic shock or severe hypotension due to bleeding and requiring pressors or surgery; clinically overt or apparent bleeding associated with a decrease in hemoglobin (Hb) of more than 5 g/dL; transfusion of 4 or more units (whole blood or packed red blood cells (PRBCs)) for bleeding.
• Major bleed – other. Any one of the following: significantly disabling (e.g., intraocular with permanent vision loss); clinically overt or apparent bleeding associated with a decrease in Hb of 3 g/dL; transfusion of 2-3 units (whole blood or PRBCs) for bleeding.
• Minor bleed. Requires medical intervention to stop or treat bleeding (e.g., epistaxis requiring visit to medical facility for packing).
• Minimal bleed. All others (e.g., bruising, bleeding gums, oozing from injection sites, etc.) not requiring intervention or treatment.

Figure 1 shows major bleeding events over time. Many events are early, at a time of coronary angiography, PCI, CABG, and other procedures, but the risk persists during later use of antiplatelet therapy.

Figure 1- Kaplan-Meier estimate of time to first PLATO-defined ‘Total Major’ bleeding event

Annualized rates of bleeding are summarized in Table 1 below. About half of the bleeding events were in the first 30 days.

As shown in Table 1, Ticagrelor was associated with a somewhat greater risk of non- CABG bleeding than was Clopidogrel. No baseline demographic factor altered the relative risk of bleeding with Ticagrelor compared to Clopidogrel.

In PLATO, 1584 patients underwent CABG surgery. The percentages of those patients who bled are shown in Table 2. Rates were very high but similar for Ticagrelor and Clopidogrel.

Although the platelet inhibition effect of Ticagrelor has a faster offset than Clopidogrel in in vitro tests and Ticagrelor is a reversibly binding P2Y12 inhibitor, PLATO did not show an advantage of Ticagrelor compared to Clopidogrel for CABG-related bleeding. When antiplatelet therapy was stopped 5 days before CABG, major bleeding occurred in 75% of Ticagrelor treated patients and 79% on Clopidogrel.

No data exist with Ticagrelor regarding a hemostatic benefit of platelet transfusions.

_{Drug Discontinuation}

In PLATO, the rate of study drug discontinuation attributed to adverse reactions was 7.4% for Ticagrelor and 5.4% for Clopidogrel. Bleeding caused permanent discontinuation of study drug in 2.3% of Ticagrelor patients and 1.0% of Clopidogrel patients. Dyspnea led to study drug discontinuation in 0.9% of Ticagrelor and 0.1% of Clopidogrel patients.

_{Common Adverse Events}

A variety of non-hemorrhagic adverse events occurred in PLATO at rates of 3% or more. These are shown in Table 3. In the absence of a placebo control, whether these are drug related cannot be determined in most cases, except where they are more common on Ticagrelor or clearly related to the drug’s pharmacologic effect (dyspnea).

_Bradycardia

In clinical studies Ticagrelor has been shown to increase the occurrence of Holter-detected bradyarrhythmias (including ventricular pauses). PLATO excluded patients at increased risk of bradycardic events (e.g., patients who have sick sinus syndrome, 2nd or 3rd degree AV block, or bradycardic-related syncope and not protected with a pacemaker). In PLATO, syncope, pre-syncope and loss of consciousness were reported by 1.7% and 1.5% of BRILINTA and Clopidogrel patients, respectively.

In a Holter substudy of about 3000 patients in PLATO, more patients had ventricular pauses with Ticagrelor (6.0%) than with Clopidogrel (3.5%) in the acute phase; rates were 2.2% and 1.6% respectively after 1 month.

_Gynecomastia

In PLATO, gynecomastia was reported by 0.23% of men on BRILINTA and 0.05% on Clopidogrel. Other sex-hormonal adverse reactions, including sex organ malignancies, did not differ between the two treatment groups in PLATO.

_{Lab abnormalities}

Serum Uric Acid:

Serum uric acid levels increased approximately 0.6 mg/dL from baseline on Ticagrelor and approximately 0.2 mg/dL on Clopidogrel in PLATO. The difference disappeared within 30 days of discontinuing treatment. Reports of gout did not differ between treatment groups in PLATO (0.6% in each group).

Serum Creatinine:

In PLATO, a >50% increase in serum creatinine levels was observed in 7.4% of patients receiving Ticagrelor compared to 5.9% of patients receiving Clopidogrel. The increases typically did not progress with ongoing treatment and often decreased with continued therapy. Evidence of reversibility upon discontinuation was observed even in those with the greatest on treatment increases. Treatment groups in PLATO did not differ for renal-related serious adverse events such as acute renal failure, chronic renal failure, toxic nephropathy, or oliguria. |postmarketing=The following adverse reactions have been identified during post-approval use of BRILINTA. Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune system disorders – Hypersensitivity reactions including angioedema. See Contraindications.

Postmarketing Experience

There is limited information about Postmarketing Experience of Ticagrelor tablet in pediatric patients.

Drug Interactions

Effects of other drugs

Ticagrelor is predominantly metabolized by CYP3A4 and to a lesser extent by CYP3A5. Ticagrelor is also a p-glycoprotein (P-gp) substrate.

• CYP3A inhibitors

• Avoid use of strong inhibitors

of CYP3A (e.g., ketoconazole, itraconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin). See Warnings and Pharmacology.

• CYP3A inducers

• Avoid use with potent inducers of CYP3A (e.g., rifampin, dexamethasone, phenytoin, carbamazepine and phenobarbital) See Contraindications, Pharmacology and Warnings.

• Aspirin

• See Pharmacology and Warnings.

Effect of ticagrelor on other drugs.

Ticagrelor is an inhibitor of CYP3A4/5 and the P-glycoprotein transporter.

• Simvastatin, lovastatin

• Brilinta will result in higher serum concentrations of [[simvastatin] and lovastatin because these drugs are metabolized by CYP3A4. Avoid simvastatin and lovastatin doses greater than 40 mg. See Pharmacology.

• Digoxin

• Digoxin: Because of inhibition of the P-glycoprotein transporter, monitor digoxin levels with initiation of or any change in ticagrelor therapy. See Pharmacology

• Other Concomitant Therapy

• BRILINTA can be administered with unfractionated or low-molecular-weight heparin, GPIIb/IIIa inhibitors, proton pump inhibitors, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers.

Use in Specific Populations

Pregnancy

• Pregnancy Category (FDA): X

• Pregnancy Category (AUS): Sandbox Ticagrelor is not included in Australian Drug Evaluation Committee (ADEC) Pregnancy Categories.

(Description)

Labor and Delivery

(Description)

Nursing Mothers

(Description)

Pediatric Use

(Description)

Geriatric Use

(Description)

Gender

(Description)

Race

(Description)

Renal Impairment

(Description)

Hepatic Impairment

(Description)

Carcinogenesis, Mutagenesis, Impairment of Fertility

(Description)

Immunocompromised Patients

(Description)

Miscellaneous

(Description)

Administration and Monitoring

Administration

(Oral/Intravenous/etc)

Monitoring

Condition 1

(Description regarding monitoring, from Warnings section)

Condition 2

(Description regarding monitoring, from Warnings section)

Condition 3

(Description regarding monitoring, from Warnings section)

IV Compatibility

Solution

Compatible

• Solution 1
• Solution 2
• Solution 3

Not Tested

• Solution 1
• Solution 2
• Solution 3

Variable

• Solution 1
• Solution 2
• Solution 3

Incompatible

• Solution 1
• Solution 2
• Solution 3

Y-Site

Compatible

• Solution 1
• Solution 2
• Solution 3

Not Tested

• Solution 1
• Solution 2
• Solution 3

Variable

• Solution 1
• Solution 2
• Solution 3

Incompatible

• Solution 1
• Solution 2
• Solution 3

Admixture

Compatible

• Solution 1
• Solution 2
• Solution 3

Not Tested

• Solution 1
• Solution 2
• Solution 3

Variable

• Solution 1
• Solution 2
• Solution 3

Incompatible

• Solution 1
• Solution 2
• Solution 3

Syringe

Compatible

• Solution 1
• Solution 2
• Solution 3

Not Tested

• Solution 1
• Solution 2
• Solution 3

Variable

• Solution 1
• Solution 2
• Solution 3

Incompatible

• Solution 1
• Solution 2
• Solution 3

TPN/TNA

Compatible

• Solution 1
• Solution 2
• Solution 3

Not Tested

• Solution 1
• Solution 2
• Solution 3

Variable

• Solution 1
• Solution 2
• Solution 3

Incompatible

• Solution 1
• Solution 2
• Solution 3

Overdosage

Acute Overdose

Signs and Symptoms

(Description)

Management

(Description)

Chronic Overdose

Signs and Symptoms

(Description)

Management

(Description)

Pharmacology

Sandbox Ticagrelor
Systematic (IUPAC) name
?
Identifiers
CAS number	?
ATC code	?
PubChem	?
Chemical data
Formula	?
Mol. mass	?
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

Mechanism of Action

(Description)

Structure

(Description with picture)

Pharmacodynamics

(Description)

Pharmacokinetics

(Description)

Nonclinical Toxicology

(Description)

Clinical Studies

Condition 1

(Description)

Condition 2

(Description)

Condition 3

(Description)

How Supplied

(Description)

• National Drug Code (NDC):
• Storage:
• Manufactured by:
• Distributed by:

Images

Drug Images

File:PILLIMAGE.jpg Drug Name: Ingredient(s): Imprint: Color(s): Shape: Size (mm): Score: Drug Label Author:

Package and Label Display Panel

(Package Images)

(Display Panel Images)

Patient Information

Patient Information from FDA

(Patient Counseling Information)

Patient Information from NLM

(Link to patient information page)

Precautions with Alcohol

Alcohol-Sandbox Ticagrelor interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

Brand Names®

Look-Alike Drug Names

• (Paired Confused Name 1a) — (Paired Confused Name 1b)
• (Paired Confused Name 2a) — (Paired Confused Name 2b)
• (Paired Confused Name 3a) — (Paired Confused Name 3b)

Drug Shortage Status

Price

References