ticagrelor

BEERS REMS

To reduce the risk of cardiovascular death, MI, and stroke in patients with acute coronary syndrome (ACS) or a history of MI. Also reduces the risk of stent thrombosis in patients who have received an intracoronary stent for ACS (in combination with aspirin).
To reduce the risk of first MI or stroke in patients with coronary artery disease who are at high risk for such events (in combination with aspirin).
To reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale score ≤5) or high-risk transient ischemic attack (TIA) (in combination with aspirin).

Action ⬆ ⬇

Both parent drug and its active metabolite inhibit platelet aggregation by reversibly interacting with platelet P2Y₁₂ADP-receptors, preventing signal transduction and platelet activation.

Therapeutic effects:

Reduction in risk of cardiovascular death, MI, and stroke associated with ACS.
Reduction in stent thrombosis
Reduction in risk of first MI or stroke in high-risk patients with coronary artery disease.
Reduction in risk of stroke in patients with acute ischemic stroke or TIA.

Pharmacokinetics ⬆ ⬇

Absorption: 36% absorbed following oral administration.

Distribution: Well distributed to tissues.

Protein Binding: 99%.

Metabolism/Excretion: Mostly metabolized in the liver by the CYP3A4 isoenzyme, with some metabolism by the CYP3A5 isoenzyme) with conversion to an active metabolite (AR-C124910XX); excretion primarily via biliary secretion; <1% excreted unchanged or as active metabolite in urine.

Half-Life: Ticagrelor: 7 hr; Active metabolite: 9 hr.

Time/Action Profile ⬆ ⬇

(inhibition of platelet aggregation)

ROUTE	ONSET	PEAK	DURATION
PO	within 30 min	4 hr	5 days‡

‡Following discontinuation.

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Active bleeding;
History of intracranial bleeding;
Severe hepatic impairment (↑ risk of bleeding);
Impending coronary artery bypass graft surgery or other surgery (discontinue 5 days prior);
Use of thrombolytics for treatment of acute ischemic stroke;
Lactation: Lactation.

Use Cautiously in:

Moderate hepatic impairment;
History of sick sinus syndrome, 2nd- or 3rd-degree heart block, or bradycardia-related syncope in the absence of a pacemaker;
Hypotension following recent coronary artery bypass graft surgery or percutaneous coronary intervention in patients receiving ticagrelor (consider bleeding as a cause);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: Safety and effectiveness not established in children;
Geri: Appears on Beers list. risk of major bleeding compared to clopidogrel, especially in patients 75 yr old. Use with caution in older adults, especially in patients 75 yr old.

Adv. Reactions/Side Effects ⬆ ⬇

CV: bradycardia, heart block

Endo: gynecomastia

Hemat: BLEEDING

Resp: dyspnea, central sleep apnea, Cheyne-Stokes respiration

Misc: HYPERSENSITIVITY REACTIONS (INCLUDING ANGIOEDEMA)

Interactions ⬆ ⬇

Drug-drug:

Strong CYP3A4/5 inhibitors, including atazanavir, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, and voriconazole, ↑ levels and the risk of bleeding; avoid concurrent use.
Strong CYP3A inducers, including carbamazepine, dexamethasone, phenobarbital, phenytoin, and rifampin, may ↓ levels and effectiveness; avoid concurrent use.
P-glycoprotein inhibitors, including cyclosporine, may ↑ levels and the risk of bleeding
Concurrent use of lovastatin or simvastatin in doses >40 mg/day ↑ risk of statin-related adverse reactions.
Effectiveness is ↓ by aspirin >100 mg/day (maintain aspirin at 75–100 mg/day).
May alter digoxin levels (monitoring recommended).
Risk of bleeding ↑ by anticoagulants, fibrinolytics, and chronic NSAIDs.
Opioids may ↓ absorption of ticagrelor and its active metabolite and ↓ antiplatelet effects; consider using parenteral antiplatelet in patients with acute coronary syndrome if concurrent use of opioids needed.

Route/Dosage ⬆ ⬇

Acute Coronary Syndrome or History of Myocardial Infarction

PO (Adults ): Loading dose: 180 mg; followed by maintenance dose: 90 mg twice daily for 1 yr, then 60 mg twice daily.

Coronary Artery Disease Without a History of Myocardial Infarction or Stroke

PO (Adults ): 60 mg twice daily.

Acute Ischemic Stroke or Transient Ischemic Attack

PO (Adults ): Loading dose: 180 mg; followed by maintenance dose: 90 mg twice daily for up to 30 days.

Availability ⬆ ⬇

(Generic available)

Tablets: 60 mg; 90 mg

Assessment ⬆ ⬇

Assess patient for symptoms of stroke, peripheral vascular disease, or MI periodically during therapy.
Observe patient for signs and symptoms of hypersensitivity reactions (rash, facial swelling, pruritus, laryngeal edema, wheezing). Discontinue drug and notify health care professional immediately if symptoms occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in case of anaphylactic reaction.

Lab Test Considerations:

May cause ↑ serum uric acid and ↑ serum creatinine.
- May cause false negative results in heparin-induced platelet aggregation assay for patients with heparin-induced thrombocytopenia.

Implementation ⬆ ⬇

PO: Administer without regard to food.
- For patients unable to swallow, tablets can be crushed and mixed with water. Mixture can also be administered via a nasogastric tube.
- Patients who have received a loading dose of clopidogrel may be started on ticagrelor.
- For acute ischemic stroke or TIA, administer a loading dose of aspirin (300–325 mg) and a daily maintenance dose of aspirin (75–100 mg) with ticagrelor.
- Discontinue ticagrelor 5 days before planned surgical procedures with a major risk of bleeding. If ticagrelor must be temporarily discontinued, restart as soon as possible. Premature discontinuation of therapy may increase risk of MI, stent thrombosis, and death.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take ticagrelor exactly as directed. Take missed doses as soon as possible unless almost time for next dose; do not double doses. Do not discontinue ticagrelor without consulting health care professional; may increase risk of cardiovascular events. Advise patient to read the Medication Guide before starting therapy and with each Rx refill in case of changes.
Advise patient that daily aspirin should not exceed 100 mg and to avoid taking other medications that contain aspirin.
Inform patient that they will bleed and bruise more easily and it will take longer to stop bleeding. Advise patient to notify health care professional promptly if unusual, prolonged, or excessive bleeding or blood in stool or urine occurs.
Inform patient that ticagrelor may cause shortness of breath, which usually resolves during therapy. Advise patient to notify health care professional if unexpected or severe shortness of breath or symptoms of hypersensitivity reactions occur.
Advise patient to notify health care professional of medication regimen prior to treatment or surgery or dental procedure. Prescriber should be consulted before stopping ticagrelor.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially aspirin or NSAIDs.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇