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Ticagrelor

Pronunciation
Pronunciation: tye-KA-grel-or
Class: Aggregation inhibitor

Trade Names

Brilinta
- Tablet, oral 90 mg

Pharmacology

Reversibly binds to the P2Y 12 class of adenosine diphosphate (ADP) receptors on platelets to prevent signal transduction and platelet activation.

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Pharmacokinetics

Absorption

T max is 1.5 h (ticagrelor) and 2.5 h (active metabolite). Absolute bioavailability is 36%. When administered with a high-fat meal, C max of ticagrelor is not affected and AUC is increased by 21%, while C max of active metabolite is decreased by 22% and AUC is unchanged. Administer without regard to food.

Distribution

Ticagrelor and the active metabolite are 99% bound to plasma proteins. Vd is 88 L (ticagrelor).

Metabolism

Metabolized to the active metabolite by CYP3A4. Ticagrelor and the active metabolite are weak substrates for P-glycoprotein (P-gp).

Elimination

26% excreted in urine (less than 1% as ticagrelor and the active metabolite); 58% excreted in feces. The half-life is 7 h (ticagrelor) and 9 h (active metabolite).

Special Populations

Renal Function Impairment

Effects of renal impairment on the pharmacokinetics are modest and do not require dose adjustment. Patients receiving dialysis have not been studied.

Hepatic Function Impairment

Effects of mild hepatic impairment on the pharmacokinetics are modest and do not require dose adjustment. Not studied in patients with moderate or severe hepatic impairment.

Elderly

Effects of age on the pharmacokinetics are modest and do not require dose adjustment.

Children

Pharmacokinetics have not been evaluated.

Gender

Effects of gender on the pharmacokinetics are modest and do not require dose adjustment.

Race

Effects of race (white or Japanese) on the pharmacokinetics are modest and do not require dose adjustment.

Smoking

Mean Cl was increased by approximately 22% in smokers; no dose adjustment is necessary.

Indications and Usage

To reduce the rate of thrombotic CV events in patients with acute coronary syndrome (ACS) (unstable angina, non-ST elevation MI, or ST elevation MI).

Contraindications

History of intracranial hemorrhage; active pathological bleeding, such as peptic ulcer or intracranial hemorrhage; severe hepatic impairment.

Dosage and Administration

Acute Coronary Syndrome
Adults

PO Start with a 180 mg loading dose, then continue at 90 mg twice daily. After the initial loading dose of aspirin, use ticagrelor with a maintenance dosage of aspirin 75 to 100 mg/day.

General Advice

  • Administer with or without food.
  • ACS patients who received a loading dose of clopidogrel may be started on ticagrelor.
  • Avoid interruptions of ticagrelor treatment. If ticagrelor must be discontinued (eg, to treat bleeding or for elective surgery), restart it as soon as possible.

Storage/Stability

Store between 59° and 86°F. Dispense in original container and keep tablets dry.

Drug Interactions

Aspirin

Use of ticagrelor with aspirin maintenance doses above 100 mg reduced the effectiveness of ticagrelor. After an initial loading dose of aspirin, use ticagrelor with aspirin 75 to 100 mg daily.

CYP3A strong inducers (eg, carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampin)

Ticagrelor plasma concentrations may be reduced, decreasing the pharmacologic effect. Avoid use with strong inducers of CYP3A.

CYP3A strong inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)

Ticagrelor plasma concentrations may be elevated, increasing the pharmacologic effects and risk of adverse reactions. Avoid concurrent use with strong inhibitors of CYP3A. Moderate CYP3A inhibitors (eg, diltiazem) have a lesser effect and dosage adjustment may not be needed.

Digoxin

Because of inhibition of the P-gp transporter, digoxin concentrations may be elevated, increasing the risk of toxicity. Monitor digoxin concentrations with initiation of, or any change in, ticagrelor therapy. Adjust the digoxin dose as needed.

Lovastatin, simvastatin

Ticagrelor will increase lovastatin and simvastatin serum concentrations because these drugs are metabolized by CYP3A4. Avoid simvastatin and lovastatin doses greater than 40 mg.

NSAIDs (eg, ibuprofen)

The risk for bleeding may be increased. If coadministration cannot be avoided, closely monitor for bleeding.

Smoking

Habitual smoking increased population mean Cl of ticagrelor approximately 22% compared with nonsmokers. No ticagrelor dose adjustment is needed based on smoking status.

Adverse Reactions

Cardiovascular

Ventricular pause (6%); atrial fibrillation, hypertension (4%); chest pain, hypotension (3%).

CNS

Headache (7%); dizziness (5%); fatigue (3%); syncope/pre-syncope/loss of consciousness (2%).

GI

Diarrhea, nausea (4%).

Hematologic

Major coronary artery bypass graft (CABG)–related bleeding (86%); non–CABG-related bleeding (9%).

Respiratory

Dyspnea (14%); cough (5%).

Miscellaneous

Increased serum creatinine (7%); back pain, noncardiac chest pain (4%).

Precautions

Warnings

Bleeding risk

Ticagrelor can cause significant, sometimes fatal, bleeding. Do not use in patients with active pathological bleeding or a history of intracranial hemorrhage. Do not start ticagrelor in patients planned to undergo urgent CABG surgery. When possible, discontinue 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, CABG, or other surgical procedures in the setting of ticagrelor. If possible, manage bleeding without discontinuing ticagrelor. Discontinuing ticagrelor increases the risk of subsequent CV events.

Aspirin dose and ticagrelor effectiveness

Maintenance doses of aspirin above 100 mg reduce the effectiveness of ticagrelor and should be avoided.


Monitor

Monitor patient for bleeding and dyspnea.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hepatic Function

Hepatic impairment increases the risk for bleeding and other adverse reactions. Consider the risks and benefits of treatment in patients with moderate hepatic impairment. Use is contraindicated in patients with severe hepatic impairment.

Dyspnea

Mild to moderate dyspnea may occur, but often resolves during continued treatment; discontinuation of therapy is not required.

Overdosage

Symptoms

Bleeding, diarrhea, nausea, ventricular pauses, vomiting.

Patient Information

  • Advise patients to read the Medication Guide prior to starting therapy and with each refill.
  • Inform patients not to discontinue ticagrelor without discussing it with their health care provider.
  • Inform patients that daily doses of aspirin should not exceed 100 mg and to avoid taking other medications that contain aspirin.
  • Inform patients that they will bleed and bruise more easily, will take longer than usual to stop bleeding, and should report any unanticipated, prolonged, or excessive bleeding, or blood in their urine or stool to health care provider without delay.
  • Inform patients that ticagrelor may cause shortness of breath. Advise them to contact their health care provider if they experience unexpected shortness of breath, especially if it is severe.
  • Advise patients to inform health care providers about use of this drug before undergoing surgical or dental procedures, and before any new drug is taken.

Copyright © 2009 Wolters Kluwer Health.

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