Brief Report: Pharmacokinetics of Crushed Elvitegravir Combination Tablet Given With or Without Enteral Nutrition

Abstract

We investigated whether a fixed-dose combination tablet of elvitegravir, cobicistat, emtricitabine, and tenofovirDF (Stribild) can be crushed and combined with enteral nutrition without influencing pharmacokinetics. This was an open-label, 3-period, single-dose, randomized, crossover trial in 24 healthy volunteers. Subjects received Stribild whole tablet with breakfast (reference), crushed/suspended Stribild + breakfast, crushed/suspended Stribild + enteral nutrition. Crushed/suspended Stribild + enteral nutrition was bioequivalent (90% confidence interval between 80% and 125%) with a whole Stribild tablet. Crushed/suspended Stribild + breakfast showed bioequivalence for the area under the curve (AUC0-32), but not for maximum concentration (Cmax) (considered not clinically relevant). Patients with swallowing difficulties or an enteral feeding tube can use crushed and suspended Stribild tablets.

Management of oral antiretroviral administration in patients with swallowing disorders or with an enteral feeding tube

“…The SODF size and shape, generic availability, oral powder or solution availability, alteration of SODF, and food considerations of the commonly used ARV drugs are summarized in Table I [12, [19][20][21][22][23][24][25][26], Table II [12, 27,28], and Table III [8,12,[29][30][31][32][33].…”

The ART of Antiretroviral Therapy in Critically Ill Patients With HIV

“…In an open label, crossover study of 24 healthy adults, the crushed combination tablet demonstrated bioequivalence (80%-125%) in regard to area under the curve (AUC) and C max when administered with enteral nutrition feeds. 90 One case report even found a sustained virologic response to the crushed combination tablet over a 4-week period. 91 In contrast, compounding a liquid formulation from the single tablet regimen of tenofovir disopoxil fumarate, emtricitabine, and efavirenz did not meet bioequivalent standards in regard to AUC and C max of efavirenz and tenofovir and the investigators recommended against crushing the combination tablet.…”

“…14 Crushing elvitegravir containing combination tablets have previously been described with similar AUC and C max compared to normal oral administration. 90 In one study of 80 HIV patients both with and without dysphagia, chewing raltegravir tablets resulted in significantly higher drug absorption and had less interpatient pharmacokinetic variability compared to swallowing tablets whole ( P = .004). 94 In regards to crushing dolutegravir tablets, two case reports have recently been published.…”

Enteral administration of crushed rilpivirine in a patient with HIV: A case report

“…Consequently, reduced drug bioavailability, especially for drugs such as rilpivirine (RPV) with complex absorption patterns, may lead to subtherapeutic concentrations, potential viral rebound and drug resistance development 1–8 . Unfortunately, there is a lack of data comparing the administration of crushed and whole tablet formulations of ART drugs 8–11 . RPV is a non‐nucleoside reverse transcriptase inhibitor with a relatively low genetic barrier to resistance compared to protease inhibitors or second‐generation integrase inhibitors, resulting in a higher risk of resistant variants in case of virological failure.…”