Dosing and uses of Brilinta (ticagrelor)
Adult dosage forms and strengths
tablet
- 60mg
- 90mg
Acute Coronary Syndrome
P2Y(12) platelet inhibitor indicated to reduce the rate of thrombotic cardiovascular events in patients with ACS (unstable angina, non-ST elevation MI, or ST elevation MI) or a history of MI
For at least the first 12 months following ACS, it is superior to clopidogreL
Ticagrelor also reduces the rate of stent thrombosis in patients who have been stented for treatment of ACs
Loading dose (following ACS event): 180 mg PO (two 90 mg tablets)
Maintenance dose (for first year following ACS event): 90 mg PO BId
Maintenance dose (after 1 year with history of MI): 60 mg PO BId
Administer with aspirin: Initial loading dose of 325 mg, then maintenance dose of aspirin of 75-100 mg/day; DO NOT exceed aspirin dose of 100 mg/day (see Black box warnings)
Dosage modifications
Renal impairment
- No dosage adjustment needed
- Dialysis: Not studied
Hepatic impairment
- Mild: No dose adjustment required
- Moderate: Data are limited; caution advised
- Severe: Not studied; avoid use due to likely increase systemic exposure to ticagrelor
Pediatric dosage forms and strengths
Safety and efficacy not established
Brilinta (ticagrelor) adverse (side) effects
>10%
Dyspnea (13.8%)
Bleeding (see specific data listed below)
1-10%
Headache (6.5%)
Cough (4.9%)
Dizziness (4.5%)
Nausea (4.3%)
Atrial fibrillation (4.2%)
Hypertension (3.8%)
Noncardiac chest pain (3.7%)
Diarrhea (3.7%)
Back pain (3.6%)
Hypotension (3.2%)
Fatigue (3.2%)
Chest pain (3.1%)
Syncope (1.7%)
<1%
Dyspena (0.9%)
Bleeding
Non-CABG related bleeds
- Total bleeds (major + minor) (8.7%)
- Major bleeds (4.5%)
- Fatal/life-threatening (2.1%)
- Fatal (0.2%)
- Intracranial (fatal/life-threatening) (0.3%)
CABG related bleeds
- Total major bleeds (85.8%)
- Major bleeds when antiplatelet therapy stopped 5 days before CABG (75%)
- Fatal/life-threatening (48.1%)
- Fatal (0.9%)
Postmarketing Reports
Immune system disorders: Hypersensitivity reactions including angioedema (see Contraindications)
Skin and subcutaneous tissue disorders: Rash
Warnings
Black box warnings
Like other antiplatelet agents, can cause significant, sometimes fatal, bleeding
Do not use with active pathological bleeding or a history of intracranial hemorrhage
Do not start in patients planned to undergo urgent coronary artery bypass graft surgery (CABG); 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 (PCI), CABG, or other surgical procedures after starting ticagrelor
If possible, manage bleeding without discontinuing; stopping ticagrelor increases risk of subsequent cardiovascular events
Aspirin dose and ticagrelor effectiveness
- Aspirin maintenance dose >100 mg reduces the effectiveness of ticagrelor and should be avoided
- After any initial loading dose, use with aspirin 75-100 mg/day
Contraindications
Hypersensitivity (eg, angioedema)
History of intracranial hemorrhage (ICH)
Active pathologic bleeding (eg, peptic ulcer, ICH)
Cautions
In clinical trials, increased overall risk of bleeding (major + minor) to a somewhat greater extent than did clopidogreL
Avoid interruption of treatment; if ticagrelor must be temporarily discontinued (eg, to treat bleeding or for elective surgery), restart as soon as possible; discontinuation will increase the risk of myocardial infarction, stent thrombosis, and death
Surgery: When possible, discontinue 5 days prior to surgery
Aspirin maintenance doses >100 mg decrease ticagrelor effectiveness; therefore, after initial aspirin loading dose (usually 325 mg), use with aspirin maintenance dose of 75-100 mg/day (see Black box warnings)
Dyspnea reported; intensity described as usually mild-to-moderate and decreases/resolves during continued treatment; If dyspnea symptoms intolerable consider administering a different antiplatelet agent
Ticagrelor can cause ventricular pauses
Bradyarrhythmias including AV block have been reported in the post- Marketing setting; Patients with a history of sick sinus syndrome, 2 nd or 3rd degree AV block or bradycardia-related syncope not protected by a pacemaker were excluded from PLATO and PEGASUS and may be at increased risk of developing bradyarrhythmias with ticagrelor
Avoid use with severe hepatic impairment, which is likely to increase ticagrelor serum levels
CYP3A4/5 substrate
- Metabolized by CYP3A4/5
- Avoid coadministration with strong CYP3A inhibitors (eg, atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)
- Avoid coadministration with potent CYP3A inducers (eg, rifampin, dexamethasone, phenytoin, carbamazepine, phenobarbital)
Pregnancy and lactation
Pregnancy category: C
In animal studies, caused structural abnormalities at maternal doses about 5-7 times the maximum recommended human dose (MRHD) based on body surface area
Should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus
Lactation: Unknown whether distributed in human breast milk; potential for serious adverse reactions in breastfed infants, a decision should be made whether to discontinue nursing or to discontinue drug, taking into account the importance of the drug to the mother
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Brilinta (ticagrelor)
Mechanism of action
Ticagrelor and its major metabolite reversibly interact with the platelet P2Y12 ADP-receptor to prevent signal transduction and platelet activation
Ticagrelor and its active metabolite are approximately equipotent
Patients can be transitioned from clopidogrel to ticagrelor without interruption of antiplatelet effect
Inhibition of platelet aggregation (IPA)
- Transitioning from clopidogrel to ticagrelor resulted in an absolute IPA increase of 26.4%
- Transitioning from ticagrelor to clopidogrel an absolute IPA decrease of 24.5%
Pharmacokinetics
Bioavailability: 36%
Peak Plasma Time: 1.5 hr; 2.5 hr (active metabolite)
Protein Bound: >99% (including active metabolite)
Vd: 88 L
Metabolized by: CYP3A4 is the major enzyme responsible for formation of its major active metabolite (AR-C124910XX); metabolized by CYP3A5 to a lesser extent
Systemic exposure to AR-C124910XX accounts for approximately 30-40%
Ticagrelor and its major active metabolite are weak P-gp substrates and inhibitors
Half-life elimination: 7 hr (ticagrelor); 9 hr (active metabolite)
Excretion (ticagrelor): feces (58%); urine (26%)
Excretion (active metabolite): Primarily by biliary excretion; urine (<1%)
Administration
Instructions
If patient has received a loading dose of clopidogrel, may be started on ticagrelor
May administer with or without food
If dose is missed, instruct patient to take one tablet (their next dose) at its scheduled time
Unable to swallow tablet whole
For patients who are unable to swallow the tablet(s) whole, tablets can be crushed, mixed with water, and drunk immediately
The glass should be refilled with water, stirred and the contents drunk to ensure the complete dose is consumed
The mixture can also be administered via a nasogastric tube (≥CH8)
It is important to flush the nasogastric tube through with water after administration of the mixture
