Ticalor Special Precautions

General Risk of Bleeding: Drugs that inhibit platelet function including Ticalor increase the risk of bleeding (see Adverse Reactions). If possible, manage bleeding without discontinuing Ticalor. Stopping Ticalor increases the risk of subsequent cardiovascular events (see Warnings, Precautions and Adverse Reactions).
Concomitant Aspirin Maintenance Dose: In PLATO, the use of Ticalor with maintenance dose of aspirin above 100 mg decreased the effectiveness of Ticalor. Therefore, after the initial loading dose of aspirin, use Ticalor with a maintenance dose of aspirin 75-100 mg (see Dosage & Administration).
Dyspnea: Dyspnea was usually mild to moderate in intensity and often resolved during continued treatment, but led to study drug discontinuation in 0.9% of Ticalor and 0.1% of clopidogrel patients in PLATO and 4.3% of Ticalor 60 mg and 0.7% on aspirin alone patients in PEGASUS. In a substudy of PLATO, 199 subjects underwent pulmonary function testing irrespective of whether they reported dyspnea. 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 patients develops new, prolonged, or worsened dyspnea that is determined to be related to Ticalor, no specific treatment is required; continue Ticalor without interruption if possible. In the case of intolerable dyspnea requiring discontinuation of Ticalor, consider prescribing another antiplatelet agent.
Discontinuation of Ticalor: Discontinuation of Ticalor will increase the risk of myocardial infarction, stroke, and death. If Ticalor must be temporarily discontinued (e.g., to treat bleeding or for significant surgery), restart it as soon as possible. When possible, interrupt therapy with Ticalor for five days prior to surgery that has a major risk of bleeding. Resume Ticalor as soon as hemostasis is achieved.
Bradyarrhythmias: Ticagrelor can cause ventricular pauses (see Adverse Reactions). Bradyarrhythmias including AV block have been reported in the postmarketing setting. Patients with a history of sick sinus syndrome, 2^nd or 3^rd 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.
Use in Hepatic Impairment: Ticagrelor is metabolized by the liver and impaired hepatic function can increase risks for bleeding and other adverse events. Avoid use of ticagrelor in patients with severe hepatic impairment. There is limited experience with Ticalor in patients with moderate hepatic impairment; consider the risks and benefits of treatment, noting the probable increase in exposure to ticagrelor. No dosage adjustment is needed in patients with mild hepatic impairment (see Warnings, Precautions and Pharmacology: Pharmacokinetics under Actions).
Severe Hepatic Impairment: Avoid use of Ticalor in patients with severe hepatic impairment. Severe hepatic impairment is likely to increase serum concentration of ticagrelor. There are no studies of ticagrelor patients with severe hepatic impairment (see Pharmacology: Pharmacokinetics under Actions).
Use in Renal Impairment: No dosage adjustment is needed in patients with renal impairment (see Pharmacology: Pharmacokinetics under Actions).
Patients with end-stage renal disease on dialysis: Clinical efficacy and safety studies with ticagrelor did not enroll patients with end-stage renal disease (ESRD) on dialysis. In patients with ESRD maintained on intermittent hemodialysis, no clinically significant difference in concentrations of ticagrelor and its metabolite and platelet inhibition are expected compared to those observed in patients with normal renal function (see Pharmacology: Pharmacokinetics under Actions). It is known whether these concentrations will lead to similar reductions in risk of CV death, myocardial infarction or stroke or similar bleeding risk in patients with ESRD on dialysis as were seen in PLATO and PEGASUS.
Use in Children: The safety and effectiveness of Ticalor in pediatric patients have not been established.
Use in the Elderly: In PLATO AND PEGASUS, about half of patients in each study were ≥65 years of age and about 15% were ≥75 years of age. No overall differences in safety or effectiveness were observed between elderly and younger patients.