Pharmacokinetic Profiles of Ticagrelor Orodispersible Tablets in Healthy Western and Japanese Subjects

Teng, Renli; Hammarberg, Maria; Carlson, Glenn; Bokelund-Singh, Sara; Ruderfelt, Terese; Blychert, Eva

doi:10.1007/s40261-017-0554-8

Cited by 10 publications

(7 citation statements)

References 47 publications

(69 reference statements)

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“…A total of 64 records were screened, of which 14 studies were selected for qualitative analysis . Among the 14 studies (Table ), 10 tested ticagrelor (crushed or chewed) alternative administration, 2 tested the effect of crushed clopidogrel, 1 of crushed prasugrel and 1 of both crushed clopidogrel and ticagrelor . Only 5 were selected for quantitative efficacy analysis, because only these studies reported PRU value at 1 h and had a control arm with standard P2Y12‐receptor inhibitor administration.…”

Section: Resultsmentioning

confidence: 99%

“…All these studies were focused on ticagrelor crushed/chewed administration. Of the remaining 9 studies excluded from quantitative analysis, but included in the systematic review, 3 lacked a control group, whereas 6 lacked of efficacy measurement (Figure ).…”

Section: Resultsmentioning

confidence: 99%

“…Conversely, the 10 studies focused on the administration of ticagrelor reported in a consistent fashion the presence of higher plasma concentration and pharmacological activity in patients treated with alternative oral administration of ticagrelor . Considering the 5 studies included in the meta‐analysis, overall 361 patients were included.…”

Section: Resultsmentioning

confidence: 99%

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Efficacy and safety of alternative oral administrations of P2Y12‐receptor inhibitors: Systematic review and meta‐analysis

Serenelli

Pavasini

Vitali

et al. 2019

Journal of Thrombosis and Haemostasis

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Background: Early administration of P2Y12-receptor inhibitors is recommended in all patients with acute coronary syndrome undergoing invasive management, with the aim to achieve the fastest and most effective platelet inhibition. Several trials investigated alternative methods of P2Y12-receptor inhibitor administration (mainly chewed or crushed) aimed at ensuring faster and higher platelet inhibition. Thus, we decided to perform a systematic review and meta-analysis analyzing efficacy and safety of alternative P2Y12-receptor inhibitor administration strategies. Methods: Systematic research was performed on Pubmed, Cochrane Library, BiomedCentral, and Web of Science databases. We included randomized or observational trials testing at least one P2Y12-receptor inhibitor alternative administration. The primary outcome of the study was the value of the platelet reactivity unit (PRU) at 1 h after drug administration, assessed by VerifyNow P2Y12 test (Accumetrics, Inc., San Diego, CA). Secondary outcomes were adverse bleeding events (safety outcome). Results and discussion:Fourteen studies were selected for qualitative analysis. Five studies, all focused on ticagrelor, were selected for quantitative efficacy analyses.These five studies compared the administration of crushed/chewed ticagrelor 180 mg loading dose (LD) with the standard whole tablets LD. The pooled mean difference between the two administrations was −59.24 PRU (95% CI from −30.61 to −87.87 PRU) in favor of the crushed/chewed administration, corresponding to a 25% mean relative PRU reduction between alternative and standard P2Y12-receptor inhibitor administrations at 1 h after drug intake. A similar relationship was found in other studies on alternative administration of clopidogrel and prasugrel, not included in the quantitative analysis. K E Y W O R D S chewed, clopidogrel, crushed, P2Y12, ticagrelor | 945 SERENELLI Et aL.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Efficacy and safety of alternative oral administrations of P2Y12‐receptor inhibitors: Systematic review and meta‐analysis

Serenelli

Pavasini

Vitali

et al. 2019

Journal of Thrombosis and Haemostasis

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“…Promising results have been described in healthy volunteers with reports of a bioequivalence between the orodispersible and the immediate release tablet. 56 Nevertheless, comparison between the orodispersible and the crushed, film-coated tablets of ticagrelor has not been performed so far.…”

Section: Crushed P2y 12 Receptor Inhibitors Tablets In Out-of-hospitamentioning

confidence: 99%

Loading with Oral P2Y12 Receptor Inhibitors: To Crush or Not to Crush?

2019

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Oral P2Y12 receptor inhibitors represent a mainstay treatment in patients with acute coronary syndrome and those undergoing percutaneous coronary intervention. In the setting of ST-elevation myocardial infarction, when early platelet inhibition is highly desirable, the onset of action of oral P2Y12 receptor inhibitors is, however, delayed, likely due to delayed drug absorption. Crushing the tablets, which are to be used for patient loading with an oral P2Y12 receptor inhibitor, has been shown to provide earlier platelet inhibition than standard, integral tablets administration. Chewed ticagrelor tablets may also result in a similar effect. Such findings should be interpreted with caution, mainly due to the small number of patients enrolled and the nature (pharmacodynamic/pharmacokinetic) of the respective studies. Furthermore, in patients with out-of-hospital cardiac arrest, who remain comatose, crushing tablets is commonly applied in clinical practice for platelet P2Y12 receptor inhibition. In this review, we focus on current evidence regarding the role of crushed P2Y12 receptor inhibitor pills, analyzing clinical scenarios where most of the promise exists along with future expectations from this type of formulation. Large randomized studies are needed to draw firm conclusions regarding the clinical benefit of ‘crushing’ over the usual ‘not-crushing’ practice.

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“…Ticagrelor has the advantage of a mortality reduction demonstrated in the PLATO trial 4 with a fast onset and offset of action 2 .Moreover, off-label use of ticagrelor is common in high-risk elective PCI such as left main stenting, stenting in diabetics, multiple stenting, high risk of stent thrombosis and lack of clopidogrel pretreatment 21 . However, this off-label use is not supported by any data.Ticagrelor validated loading dose in PCI for ACS is 180 mg with oral administration (2 tablets of 90 mg) or with crushed or orodispersible tablets27,28 followed by 90 mg twice daily maintenance dose (MD) was chosen at the time of design of the ALPHEUS trial. Beside the ISAR-REACT 5 trial 29 recently published and conducted in an ACS population, there is no trial that compared ticagrelor to prasugrel in the setting of elective PCI.…”

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confidence: 99%

Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study

Silvain

Cayla

Beygui

et al. 2020

American Heart Journal

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Background Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggest that PCI related myocardial infarction (MI) and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y 12 receptor inhibitor such as ticagrelor, may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy (DAPT) by aspirin and clopidogrel in this setting. Methods ALPHEUS (Assessment of Loading with the P2Y 12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) (NCT02617290) is an international, multicenter, randomized, parallel-group, open label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180mg or a loading dose of clopidogrel (300 or 600mg) in addition to aspirin. Patients will then receive a DAPT with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75mg once daily for 30 days. The primary ischemic endpoint is PCI-related myocardial infarction (MI type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (BARC type 3 or 5) at 48 hours (or discharge if it occurs earlier). Conclusion ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate endpoint for mortality. RCT# NCT02617290

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Pharmacokinetic Profiles of Ticagrelor Orodispersible Tablets in Healthy Western and Japanese Subjects

Cited by 10 publications

References 47 publications

Efficacy and safety of alternative oral administrations of P2Y12‐receptor inhibitors: Systematic review and meta‐analysis

Efficacy and safety of alternative oral administrations of P2Y12‐receptor inhibitors: Systematic review and meta‐analysis

Loading with Oral P2Y12 Receptor Inhibitors: To Crush or Not to Crush?

Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study

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