Evaluation of Crushed Ticagrelor Tablet Doses: Recovery Following Crushing and Naso-gastric Tube Passage Ex Vivo

Abstract

BackgroundOrally available ticagrelor in combination with low-dose aspirin (75–100 mg/day) is indicated for adult patients with acute coronary syndromes. However, patients with swallowing difficulties may be unable to consume the currently available 90-mg tablet. It is hypothesized that ticagrelor could be given to this patient cohort as a crushed dose administered either orally or via a naso-gastric (NG) tube.ObjectivesTo investigate the potential use of crushed ticagrelor tablets (90- and 180-mg doses) for oral dose or NG tube administration.MethodsTicagrelor tablets (90 or 180 mg [two 90-mg tablets]) were prepared to emulate oral and NG tube administration by similar methods. For the oral dose, ticagrelor tablets were crushed using a mortar and pestle and transferred to a dosing cup. 100 mL of water was added to the mortar, stirred, and the contents were transferred to the dosing cup and stirred to form a suspension. At this stage, where the suspension would normally be administered to a patient, it was collected for high performance liquid chromatography (HPLC) analysis. The mortar was then flushed with 100 mL of water, and the contents were again transferred to the dosing cup, stirred, and collected for HPLC analysis. For the NG dose, polyvinylchloride, polyurethane, and silicone size CH10 NG tubes were used. The tablets were crushed using a mortar and pestle, diluted with 50 mL of water, and stirred. At this stage, where the suspension would normally be administered to a patient through an NG tube using a syringe, it was collected for HPLC analysis. The mortar was then flushed with two additional 50 mL aliquots of water and the contents were passed through the NG tube. HPLC analysis examined the recoverability of ticagrelor in each of the dose suspensions and flushes and the stability of the suspension when held in a syringe for up to 2 h.ResultsOne or two crushed 90-mg ticagrelor tablets, prepared for either oral or NG tube administration, delivers a mean dose of ≥97 % of the original tablet. No degradation of the suspensions was detected after ticagrelor had been held in the syringe for up to 2 h.ConclusionAlthough not an approved method of administration, these results suggest that ticagrelor tablets can be crushed and prepared for oral administration or for administration via an NG tube. From a clinical perspective, a syringe hold-time of up to 2 h should allow for enough time between preparation and administration (orally or via an NG tube) of the dispersed tablets to the patient. Future studies are required to test the effect of crushed dosing on pharmacokinetic and pharmacodynamic parameters.

Comparison of Active Substance Losses and Total Weight Losses of Tablets Administered Via Feeding Tube

“…They found that ≥97% of the active substance from one original tablet is delivered through the NGT. However, this study is limited by the high volume of water for flushing the mortar and the NGT (150 mL), which is often inapplicable in critical care [4]. On the other hand, Kotake et al [5] found that approximately 30% of amiodarone from tablets is lost during administration via NGT.…”

“…Crean et al [4] conducted an ex vivo study investigating the administration of crushed ticagrelor tablets via NGT. They found that ≥97% of the active substance from one original tablet is delivered through the NGT.…”

The influence of metoclopramide on pharmacokinetics and pharmacodynamics of ticagrelor in patients with unstable angina pectoris receiving concomitant treatment with morphine — a protocol of a randomized trial

“…Previously reported studies showed that the administration of crushed ticagrelor increased both ticagrelor and its active metabolite concentration in human plasma [11,12]. Additionally, in patients treated with crushed ticagrelor, earlier inhibition of platelet aggregation was observed, compared to the reports in which the integral tablets were given [13,14].…”

Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets

“…(9,10) Recently, crushed ticagrelor tablets, administered orally or via a naso-gastric tube, has been shown to be feasible and resulted in increased plasma concentration of ticagrelor and its active metabolite at an earlier time point compared to integral tablets. (11,12) As the plasma concentration of ticagrelor and its active metabolite is linearly associated with the degree of platelet inhibition, (2) administration of crushed or chewed ticagrelor may provide a more rapid onset of drug action. Nevertheless, limited pharmacodynamic data of novel methods of ticagrelor administration exist and data regarding chewed ticagrelor have not been reported.…”