ing events that occurred on ZONTIVITY were treated in the same manner as for other antiplatelet agents.
Use in Patients with History of Stroke, TIA, or ICH
In the TRA 2°P study, patients with a history of ischemic stroke had a higher rate for ICH on ZONTIVITY than on placebo. ZONTIVITY is contraindicated in patients with a history of stroke, TIA, or ICH [see Contraindications (4)].
Other Adverse Reactions
Adverse reactions other than bleeding were eva luated in 19,632 patients treated with ZONTIVITY [13,186 patients in the TRA 2°P study and 6,446 patients in the TRA•CER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) study]. Adverse events other than bleeding that occurred at a rate that was at least 2% in the ZONTIVITY group and also 10% greater than the rate in the placebo group are shown in Table 2.
Table 2: TRA 2°P / TRA•CER — Percentage of Patients Reporting Non-hemorrhagic Adverse Reactions at a Rate at Least 2% in the ZONTIVITY Group and at Least 10% Greater than Placebo
The following adverse reactions occurred at a rate less than 2% in the ZONTIVITY group but at least 40% greater than placebo. In descending order of rate in the ZONTIVITY group: iron deficiency, retinopathy or retinal disorder, and diplopia/oculomotor disturbances.
An increased rate of diplopia and related oculomotor disturbances was observed with ZONTIVITY treatment (30 subjects, 0.2%) vs. placebo (10 subjects, 0.06%). While some cases resolved during continued treatment, information on resolution of symptoms was not available for some cases.
7 DRUG INTERACTIONS
7.1 Effects of Other Drugs on ZONTIVITY
Vorapaxar is eliminated primarily by metabolism, with contributions from CYP3A4 and CYP2J2.
Strong CYP3A Inhibitors
Avoid concomitant use of ZONTIVITY with strong inhibitors of CYP3A (e.g., ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin and conivaptan) [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].
with strong inducers of CYP3A (e.g., rifampin, carbamazepine, St. John’s Wort and phenytoin) [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category B
There are no adequate and well-controlled studies of ZONTIVITY use in pregnant women.
Risk Summary
Based on data in rats and rabbits, ZONTIVITY is predicted to have a low probability of increasing the risk of adverse developmental outcomes above background. No embryo/fetal toxicities, malformations or maternal toxicities were observed in rats exposed during gestation to 56 times the human systemic exposure at the recommended human dose (RHD). No embryo/fetal toxicities, malformations or maternal toxicities were observed in rabbits exposed during gestation to 26 times the human systemic exposure at the RHD. The No Adverse Effect Level (NOAEL) for decreased perinatal survival and body weight in off-spring exposed in utero and during lactation was 31 times the human systemic exposure at the RHD. Both male and female pups displayed transient effects on sensory function and neurobehavioral development at weaning at 67 times the human exposure at the RHD, whereas female pups displayed decreased memory at 31 times the human exposure at the RHD. However, animal studies are not always predictive of a human response. ZONTIVITY shou |
