Castella 90

Castella 90  contains Ticagrelor, a member of the chemical class cyclopentyl-triazolopyrimidines (CPTP), which is an oral, direct acting, selective and reversibly binding P2Y12 receptor antagonist that prevents ADP-mediated P2Y12 dependent platelet activation and aggregation.

Pack size Box of 30 tablets, 60 tablets
Shelf-life 24 months
Composition Ticagrelor
Dosage forms and strengths Film-coated tablet: 90 mg
Product code :



Ticagrelor, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with:

  • Acute coronary syndromes (ACS).
  • A history of myocardial infarction (MI) and a high risk of developing an atherothrombotic event.


Patients taking ticagrelor should also take a daily low maintenance dose of ASA 75 – 150 mg, unless specifically contraindicated.

  • Acute coronary syndromes
    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.
    Treatment with ticagrelor 90 mg twice daily is recommended for 12 months in ACS patients unless discontinuation is clinically indicated.
  • History of myocardial infarction (MI)
    Ticagrelor 60 mg twice daily is the recommended dose when an extended treatment is required for patients with a history of MI of at least one year and a high risk of an atherothrombotic event.
    Treatment may be started without interruption as continuation therapy after the initial one-year treatment with ticagrelor 90 mg or other adenosine diphosphate (ADP) receptor inhibitor therapy in ACS patients with a high risk of an atherothrombotic event.
    Treatment can also be initiated up to 2 years from the MI, or within one year after stopping previous ADP receptor inhibitor treatment.
    There are limited data on the efficacy and safety of ticagrelor beyond 3 years of extended treatment. If a switch is needed, the first dose of ticagrelor should be administered 24 hours following the last dose of the other antiplatelet medication.
  • Missed dose
    Lapses in therapy should also be avoided. A patient who misses a dose of ticagrelor should take only one tablet (their next dose) at its scheduled time.

Special populations

  • No dose adjustment is required in elderly.
  • No dose adjustment is necessary for patients with renal impairment.
  • Hepatic impairment
    Ticagrelor has not been studied in patients with severe hepatic impairment and its use in these patients is therefore contraindicated. Only limited information is available in patients with moderate hepatic impairment. Dose adjustment is not recommended, but ticagrelor should be used with caution. No dose adjustment is necessary for patients with mild hepatic impairment.
  • The safety and efficacy of ticagrelor in children below the age of 18 years have not been established.


  • Ticagrelor is administered orally, with or without food.
  • For patients who are unable to swallow the tablet(s) whole, the tablets can be crushed to a fine powder and mixed in half a glass of water and drunk immediately. The glass should be rinsed with a further half glass of water and the contents drunk. The mixture can also be administered via a nasogastric tube (CH8 or greater). It is important to flush the nasogastric tube through with water after administration of the mixture.
  • Hypersensitivity to the active substance or to any of the excipients.
  • Active pathological bleeding.
  • History of intracranial haemorrhage.
  • Severe hepatic impairment.
  • Co-administration of ticagrelor with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, nefazodone, ritonavir and atazanavir), as co-administration may lead to a substantial increase in exposure to ticagrelor.

Very common

  • Blood disorder bleedings (e.g. increased tendency to bruise, spontaneous haematoma, haemorrhagic diathesis).
  • Hyperuricaemia.
  • Dyspnoea.


  • Gout/Gouty arthritis.
  • Dizziness, syncope, headache.
  • Vertigo.
  • Hypotension.
  • Respiratory system bleedings (e.g. epistaxis, haemoptysis).
  • Subcutaneous or dermal bleeding (e.g. ecchymosis, skin haemorrhage, petechiae), rash, pruritus.
  • Urinary tract bleeding (e.g. haematuria, cystitis haemorrhagic).
  • Blood creatinine increased.
  • Post procedural haemorrhage, traumatic bleedings (e.g. contusion, traumatic haematoma, traumatic haemorrhage).

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). The use of ticagrelor is contraindicated in patients with active pathological bleeding, in those with a history of intracranial haemorrhage, and in patients with severe hepatic impairment.
    – Patients with concomitant administration of medicinal products that may increase the risk of bleeding (e.g. nonsteroidal anti-inflammatory drugs (NSAIDs), oral anticoagulants and/or fibrinolytics) within 24 hours of ticagrelor dosing.
  • Platelet transfusion did not reverse the antiplatelet effect of ticagrelor in healthy volunteers and is unlikely to be of clinical benefit in patients with bleeding. Since co-administration of ticagrelor with desmopressin did not decrease template-bleeding time, desmopressin is unlikely to be effective in managing clinical bleeding events.
  • 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.


  • 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.
  • In PLATO patients undergoing coronary artery bypass grafting (CABG), ticagrelor had more bleeding than clopidogrel when stopped within 1 day prior to surgery but a similar rate of major bleeds compared to clopidogrel after stopping therapy 2 or more days before surgery. If a patient is to undergo elective surgery and 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 (PLATO study).
  • Treatment beyond one year is not recommended in patients with history of MI with prior ischaemic stroke.

Hepatic impairment

  • Use of ticagrelor is contraindicated in patients with severe hepatic impairment.
  • Caution is advised in patients with moderate hepatic impairment.

Patients at risk for bradycardic events

  • Holter ECG monitoring has shown an increased frequency of mostly asymptomatic ventricular pauses during treatment with ticagrelor compared with clopidogrel. Patients with an increased risk of bradycardic events (e.g. patients without a pacemaker who have sick sinus syndrome, 2nd or 3rd degree AV block or bradycardic-related syncope) have been excluded from the main studies evaluating the safety and efficacy of ticagrelor. Therefore, due to the limited clinical experience, ticagrelor should be used with caution in these patients.
  • Caution should be exercised when administering ticagrelor concomitantly with medicinal products known to induce bradycardia. However, no evidence of clinically significant adverse reactions was observed in the PLATO trial after concomitant administration with one or more medicinal products known to induce bradycardia (e.g. 96% beta blockers, 33% calcium channel blockers diltiazem and verapamil and 4% digoxin).
  • During the Holter substudy in PLATO, more patients had ventricular pauses ≥ 3 seconds with ticagrelor than with clopidogrel during the acute phase of their ACS. The increase in Holter-detected ventricular pauses with ticagrelor was higher in patients with chronic heart failure (CHF) than in the overall study population during the acute phase of ACS, but not at one month with ticagrelor or compared to clopidogrel. There were no adverse clinical consequences associated with this imbalance (including syncope or pacemaker insertion) in this patient population.


  • Dyspnoea was reported in patients treated with ticagrelor. Dyspnoea is usually mild to moderate in intensity and often resolves without need for treatment discontinuation. 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 history of asthma and/or COPD. The mechanism has not been elucidated. If a patient reports new, prolonged or worsened dyspnoea this should be investigated fully and if not tolerated, treatment with ticagrelor should be stopped.

Creatinine elevations

  • Creatinine levels may increase during treatment with ticagrelor. The mechanism has not been elucidated. Renal function should be checked according to routine medical practice. In patients with ACS, it is recommended that renal function is also checked one month after initiating the treatment with ticagrelor and then according to routine medical practice, 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 history of hyperuricaemia or gouty arthritis. As a precautionary measure, the use of ticagrelor in patients with uric acid nephropathy is discouraged.

Thrombotic Thrombocytopenic Purpura (TTP) has been reported very rarely with the use of ticagrelor. It is characterised by thrombocytopenia and microangiopathic haemolytic anaemia associated with either neurological findings, renal dysfunction or fever. TTP is a potentially fatal condition requiring prompt treatment including plasmapheresis.

Interference with platelet function tests to diagnose heparin induced thrombocytopenia (HIT)

  • In the heparin induced platelet activation (HIPA) test used to diagnose HIT, anti-platelet factor 4/heparin antibodies in patient serum activate platelets of healthy donors in the presence of heparin.
  • False negative results in a platelet function test (to include, but may not be limited to the HIPA test) for HIT have been reported in patients administered ticagrelor. This is related to inhibition of the P2Y12-receptor on the healthy donor platelets in the test by ticagrelor in the patient’s sera/plasma. Information on concomitant treatment with ticagrelor is required for interpretation of HIT platelet function tests.
  • In patients who have developed HIT, the benefit-risk of continued treatment with ticagrelor should be assessed, taking both the prothrombotic state of HIT and the increased risk of bleeding with concomitant anticoagulant and ticagrelor treatment into consideration.


  • Based on a relationship observed in PLATO between maintenance ASA dose and relative efficacy of ticagrelor compared to clopidogrel, co-administration of ticagrelor and high maintenance dose ASA (> 300 mg) is not recommended.
  • Premature discontinuation with any antiplatelet therapy, including ticagrelor, could result in an increased risk of cardiovascular (CV) death, MI or stroke due to the patient’s underlying disease. Therefore, premature discontinuation of treatment should be avoided.
  • Women of childbearing potential should use appropriate contraceptive measures to avoid pregnancy during ticagrelor therapy.
  • Ticagrelor is not recommended during pregnancy.
  • Lactation: A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from ticagrelor therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
  • During treatment with ticagrelor, dizziness and confusion have been reported. Therefore, patients who experience these symptoms should be cautious while driving or using machines.