Marieke Roskam-Kwint1,2, Pauline Bollen1, Angela Colbers1, Marjolijn Duisenberg-van Essenberg2, Veroniek Harbers3, David Burger1. 1. Department of Pharmacy, Radboud Institute for Health Sciences, Radboud university medical center, Nijmegen, The Netherlands. 2. Department of Pharmacy, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands. 3. Clinical Research Centre Nijmegen, Radboud university medical center, Nijmegen, The Netherlands.
Abstract
Background: If HIV patients are unconscious or cannot swallow tablets for other reasons, antiretroviral medication is crushed and dissolved prior to administration. Crushing can alter drug exposure, possibly leading to treatment failure, development of resistance or toxicity. Currently, there is no information about crushing of the branded fixed-dose combination of dolutegravir/abacavir/lamivudine (Triumeq®, referred to as TRI); therefore, crushing of TRI is not recommended. Objectives: To investigate whether the TRI fixed-dose combination tablet can be crushed and combined with enteral nutrition without influencing pharmacokinetics (PK). Methods: We carried out an open-label, three-period, randomized, single-dose, crossover trial in 22 healthy adult volunteers. Subjects randomly received whole-tablet TRI with fasting (reference), crushed and suspended TRI with fasting or crushed and suspended TRI with oral intake of enteral nutrition. Bioequivalence criteria (80%-125% acceptance range) of AUC0-∞ and Cmax were used. ClinicalTrials.gov: NCT02569346. Results: Crushing TRI leads to higher dolutegravir exposure (AUC0-∞: +26% and Cmax: +30%) and, if crushed TRI is combined with enteral nutrition, to a decrease in abacavir Cmax (-17%). Lamivudine concentrations were not affected as geometric mean ratios with 90% CIs fell within the 80%-125% range. Conclusions: Bioequivalence could not be demonstrated for a crushed and suspended tablet or a crushed and suspended tablet with oral intake of enteral nutrition compared with whole-tablet TRI with fasting. Both scenarios led to higher dolutegravir exposure, but this did not exceed exposure after intake with food or in twice-daily dosing. In our opinion, TRI can be crushed for patients with swallowing difficulties and can be simultaneously administered with enteral nutrition.
Background: If HIV patients are unconscious or cannot swallow tablets for other reasons, antiretroviral medication is crushed and dissolved prior to administration. Crushing can alter drug exposure, possibly leading to treatment failure, development of resistance or toxicity. Currently, there is no information about crushing of the branded fixed-dose combination of dolutegravir/abacavir/lamivudine (Triumeq®, referred to as TRI); therefore, crushing of TRI is not recommended. Objectives: To investigate whether the TRI fixed-dose combination tablet can be crushed and combined with enteral nutrition without influencing pharmacokinetics (PK). Methods: We carried out an open-label, three-period, randomized, single-dose, crossover trial in 22 healthy adult volunteers. Subjects randomly received whole-tablet TRI with fasting (reference), crushed and suspended TRI with fasting or crushed and suspended TRI with oral intake of enteral nutrition. Bioequivalence criteria (80%-125% acceptance range) of AUC0-∞ and Cmax were used. ClinicalTrials.gov: NCT02569346. Results: Crushing TRI leads to higher dolutegravir exposure (AUC0-∞: +26% and Cmax: +30%) and, if crushed TRI is combined with enteral nutrition, to a decrease in abacavir Cmax (-17%). Lamivudine concentrations were not affected as geometric mean ratios with 90% CIs fell within the 80%-125% range. Conclusions: Bioequivalence could not be demonstrated for a crushed and suspended tablet or a crushed and suspended tablet with oral intake of enteral nutrition compared with whole-tablet TRI with fasting. Both scenarios led to higher dolutegravir exposure, but this did not exceed exposure after intake with food or in twice-daily dosing. In our opinion, TRI can be crushed for patients with swallowing difficulties and can be simultaneously administered with enteral nutrition.
Authors: M de Antonio-Cuscó; F J Parrilla; H Knobel Freud; D Echeverría-Esnal; A Castellví Font; A Vázquez; J R Masclans; O Ferrández; S Grau Journal: Rev Esp Quimioter Date: 2022-05-30 Impact factor: 2.515
Authors: Daniëlle W M Pijnenburg; Minou van Seyen; Evertine J Abbink; Angela Colbers; Joost P H Drenth; David M Burger Journal: J Antimicrob Chemother Date: 2020-09-01 Impact factor: 5.758