Brilinta (ticagrelor)

Brilinta is a P2Y12 platelet inhibitor indicated to reduce the rate of for cardiovascular death, myocardial infarction, and stroke in patients with acute coronary syndrome (ACS) or a history of myocardial infarction (MI). For at least the first 12 months following ACS, it is superior to clopidogrel. Brilinta also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACS.

General Risk of Bleeding

Drugs that inhibit platelet function including Brilinta increase the risk of bleeding. If possible, manage bleeding without discontinuing Brilinta. Stopping Brilinta increases the risk of subsequent cardiovascular events

Concomitant Aspirin Maintenance Dose

In PLATO the use of Brilinta with maintenance doses of aspirin above 100 mg decreased the effectiveness of Brilinta. Therefore, after the initial loading dose of aspirin, use Brilinta with a maintenance dose of aspirin of 75-100 mg

Dyspnea

In clinical trials, about 14% of patients treated with Brilinta developed dyspnea. Dyspnea was usually mild to moderate in intensity and often resolved during continued treatment. There was no indication of an adverse effect on pulmonary function assessed after one month or after at least 6 months of chronic treatment. If a patient develops new, prolonged, or worsened dyspnea that is determined to be related to Brilinta, no specific treatment is required; continue Brilinta without interruption if possible. In the case of intolerable dyspnea requiring discontinuation of Brilinta, consider prescribing another antiplatelet agent.

Discontinuation of Brilinta

Discontinuation of Brilinta will increase the risk of myocardial infarction, stroke, and death. If Brilinta must be temporarily discontinued (e.g., to treat bleeding or for significant surgery), restart it as soon as possible. When possible, interrupt therapy with Brilinta for five days prior to surgery that has a major risk of bleeding. Resume Brilinta as soon as hemostasis is achieved.

Severe Hepatic Impairment

Avoid use of Brilinta in patients with severe hepatic impairment. Severe hepatic impairment is likely to increase serum concentration of ticagrelor. There are no studies of Brilinta patients with severe hepatic impairment

What is the dosage of ticagrelor?

Initiate treatment with 180 mg oral loading dose following an ACS event. Brilinta safely and effectively. See full prescribing information for Continue treatment with 90 mg twice daily during the first year after an ACS Brilinta. event. After one year, administer 60 mg twice daily. Use Brilinta with a daily maintenance dose of aspirin of 75-100 mg.

Initiate treatment with 180 mg oral loading dose following an ACS event. Brilinta safely and effectively. See full prescribing information for Continue treatment with 90 mg twice daily during the first year after an ACS Brilinta. event. After one year, administer 60 mg twice daily. Use Brilinta with a daily maintenance dose of aspirin of 75-100 mg.

Strong CYP3A Inhibitors

Strong CYP3A inhibitors substantially increase ticagrelor exposure and so increase the risk of dyspnea, bleeding, and other adverse events. Avoid use of strong inhibitors of CYP3A (e.g.,

• ketoconazole,
• itraconazole,
• voriconazole,
• clarithromycin,
• nefazodone,
• ritonavir,
• saquinavir,
• nelfinavir,
• indinavir,
• atazanavir and
• telithromycin)

Strong CYP3A Inducers

Strong CYP3A inducers substantially reduce ticagrelor exposure and so decrease the efficacy of ticagrelor. Avoid use with strong inducers of CYP3A (e.g.,

• rifampin,
• phenytoin,
• carbamazepine and
• phenobarbital).

Aspirin

Use of Brilinta with aspirin maintenance doses above 100 mg reduced the effectiveness of Brilinta

Simvastatin, Lovastatin

Brilinta increases serum concentrations of simvastatin and lovastatin because these drugs are metabolized by CYP3A. Avoid simvastatin and lovastatin doses greater than 40 mg.

Digoxin

Brilinta inhibits the P-glycoprotein transporter; monitor digoxin levels with initiation of or change in Brilinta therapy

There are no adequate and well-controlled studies of Brilinta use in pregnant women. In animal studies, ticagrelor caused structural abnormalities at maternal doses about 5 to 7 times the maximum recommended human dose (MRHD) based on body surface area. Brilinta should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is not known whether ticagrelor or its active metabolites are excreted in human milk. Ticagrelor is excreted in rat milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from Brilinta, a decision should be made whether to discontinue nursing or to discontinue Brilinta.