Dosage Form: Tablet
Ticagrelor is indicated for the prevention of atherothrombotic events in adult patients with Acute Coronary Syndromes (unstable angina, non ST elevation Myocardial Infarction [NSTEMI] or ST elevation Myocardial Infarction [STEMI]); including patients managed medically, and those who are managed with percutaneous coronary intervention (PCI) or coronary artery by-pass grafting (CABG).
Ticagrelor is a selective adenosine diphosphate (ADP) receptor antagonist acting on the P2Y12 ADP-receptor that can prevent ADP-mediated platelet activation and aggregation. Ticagrelor reversibly interacts with the platelet P2Y12 ADP-receptor.Ticagrelor does not interact with the ADP binding site itself, but interacts with platelet P2Y12 ADP-receptor to prevent signal transduction.Thus it prevents platelet activation & aggregation.
Dosage guidelines: T
Ticagrelor treatment should be initiated with a single 180 mg loading dose (two tablets of 90 mg) and then continued at 90 mg twice daily. Patients taking Ticagrelor should also take aspirin daily, unless specifically contraindicated. Following an initial dose of aspirin (usually 325 mg), Ticagrelor should be used with a maintenance dose of aspirin of 75-100 mg. Maintenance dose of Aspirin above 100 mg decreased the efficacy of Ticagrelor. So, maintenance dose of aspirin above 100 mg should be avoided.
A patient who misses a dose of Ticagrelor should take only one 90 mg tablet (the next dose) at its scheduled time. Patients treated with Clopidogrel can be directly switched to Ticagrelor if needed. Switching from prasugrel to ticagrelor has not been investigated.
Treatment is recommended for up to 12 months unless discontinuation of Ticagrelor is clinically indicated. Ticagrelor can be administered with or without food.
Route of administration: Orally.
CYP3A inhibitors: Avoid use of strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir and telithromycin).
CYP3A inducers: Avoid use with potent inducers of CYP3A (e.g., rifampin, dexamethasone, phenytoin,carbamazepine and phenobarbital).
Aspirin: Use of Ticagrelor with aspirin maintenance doses above 100 mg reduced the effectiveness ofTicagrelor.
Simvastatin, Lovastatin: Ticagrelor 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.
Digoxin: Because of inhibition of the P-glycoprotein transporter, monitor digoxin levels with initiation of or any change in ticagrelor therapy.
Other Concomitant Therapy: Ticagrelor can be administered with unfractionated or low-molecular-weight heparin, GPIIb/llla inhibitors, proton pump inhibitors, beta-blockers, angiotensin converting enzyme inhibitors, and angiotensin receptor blockers.
Ticagrelor is contraindicated in case of-
- Hypersensitivity to Ticagrelor or to any of the excipients
- Active pathological bleeding (peptic ulcer)
- History of intracranial haemorrhage
- Moderate to severe hepatic impairment
- Co-administration of Ticagrelor with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, nefazodone, ritonavir, and atazanavir)
Very Common: Blood disorder bleedings, Hyperuricaemia, Dyspnoea.
Common: Gout/Gouty Arthritis, Dizziness, Syncope, Headache, Vertigo, Hypotension, Respiratory system bleedings, Gastrointestinal haemorrhage, Diarrhoea, Nausea, Dyspepsia, Constipation, Subcutaneous or dermal bleeding, Rash, Pruritus, Urinary tract bleeding, Blood creatinine increased, Postprocedural haemorrhage, Traumatic bleedings.
Uncommon: Tumour bleedings, Hypersensitivity including angioedema, Confusion, Intracranial haemorrhage, Eye haemorrhage, Ear haemorrhage, Retroperitoneal haemorrhage, Muscular bleedings.
Pregnancy & Lactation:
Pregnancy category C. There are no or limited amount of data from the use of Ticagrelor in pregnant women.Ticagrelor is not recommended during pregnancy. Available pharmacodynamic/toxicological data in animals have shown excretion of Ticagrelor and its active metabolites in milk. A risk to newborns/infants cannot be excluded. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from ticagrelor therapy taking into account the benefit of breastfeeding for the child and the benefit of therapy for the women.
Precautions & Warnings:
Bleeding risk: The use of ticagrelor in patients at known increased risk for bleeding should be balanced against the benefit in terms of prevention of atherothrombotic events. If clinically indicated, ticagrelor should be used with caution in the following patient groups; Patients with a propensity to bleed (e.g. due to recent trauma, recent surgery, coagulation disorders, active or recent gastrointestinal bleeding). Antifibrinolytic therapy (aminocaproic acid or tranexamic acid) and/or recombinant factor VIIa therapy may increase haemostasis. Ticagrelor may be resumed after the cause of bleeding has been identified and controlled.
Surgery: Patients should be advised to inform physicians and dentists that they are taking ticagrelor before any surgery is scheduled and before any new medicinal product is taken. If a patient is to undergo elective surgery and the antiplatelet effect is not desired, ticagrelor should be discontinued 5 days prior to surgery.
Patients with prior ischaemic stroke: ACS patients with prior ischaemic stroke can be treated with ticagrelor for up to 12 months. Patients at risk for bradycardic events: Due to the limited clinical experience, ticagrelor should be used with caution in these patients.
Dyspnoea: Patients with asthma/chronic obstructive pulmonary disease (COPD) may have an increased absolute risk of experiencing dyspnoea with ticagrelor. Ticagrelor should be used with caution in patients with a history of asthma and/or COPD. Creatinine elevations: Creatinine levels may increase during treatment with ticagrelor. In patients with ACS, it is recommended that renal function is also checked one month after initiating the treatment with ticagrelor, paying special attention to patients ≥75 years, patients with moderate/severe renal impairment and those receiving concomitant treatment with an angiotensin receptor blocker (ARB). Uric acid increase: Hyperuricaemia may occur during treatment with ticagrelor. Caution is advised in patients with a history of hyperuricaemia or gouty arthritis. Other: Based on a relationship observed in PLATO between maintenance dose of acetylsalicylic acid (ASA) and relative efficacy of ticagrelor compared to clopidogrel, co-administration of ticagrelor and high maintenance dose of acetylsalicylic acid (ASA) (>300 mg) is not recommended.
Premature discontinuation: Premature discontinuation with any antiplatelet therapy, including ticagrelor, could result in an increased risk of cardiovascular (CV) death or MI due to the patient’s underlying disease. Therefore, premature discontinuation of treatment should be avoided.
Pediatric Use: The safety and effectiveness of Ticagrelor in pediatric patients have not been established.
Geriatric Use: No overall differences in safety or effectiveness were observed in geriatric patients.
Hepatic Impairment: Ticagrelor has not been studied in the patients with moderate or severe hepatic impairment. Ticagrelor is metabolized by the liver and impaired hepatic function can increase risks for bleeding and other adverse events. Hence,
Renal Impairment: No dosage adjustment is needed in patients with renal impairment. Patients receiving dialysis have not been studied.
Store in a cool & dry place, protected from light. Keep all medicines out of reach of children.
Manufactured by: Ziska Pharmaceuticals Ltd.