Can Biktarvy be crushed and given via tube feed to intubated patients?

Comment by InpharmD Researcher

There is conflicting evidence on whether bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) may be crushed for tube administration. The product’s labeling states the tablet can be split and each portion taken separately as long as all parts are ingested within ten minutes. A search of clinical literature identified four case reports (see summary and tables 1-3). Two cases reported successful viral suppression when administered via percutaneous endoscopic gastrostomy (PEG) tube. One of these cases described the fixed-dose tablet was pulverized and then mixed with 30 to 60 mL before administering. Another case describes a patient who, without healthcare practitioner consultation, dissolved the tablet in a tablespoonful of orange juice (with no manipulation), waited for approximately 10 minutes, and swallowed the drug but maintained virologic suppression. A final case reported potential resistance when Biktarvy was administered through NG tubing. Due to conflicting evidence, consider a patient’s current viral load, previous response history, and anticipated duration of tubal support in conjunction with consulting a patient’s HIV care provider.

Pubmed: bictegravir crush = 2 results (2 relevant) Pubmed: bictegravir/emtricitabine/tenofovir alafenamide nasogastric = 1 result (1 relevant) Pubmed: bictegravir tube = 6 results (1 new relevant) Pubmed: bictegravir PEG = no new results

Background

Biktarvy is not listed on the Insitute for Safe Medication Practices (ISMP) “Do Not Crush” list. [1]

According to guidelines for the use of antiretroviral agents in adults and adolescents living with HIV, discontinuation or planned interruption of antiretroviral therapy (ART) is not recommended outside the context of a clinical trial, however, unplanned interruption of ART may occur under certain circumstances, including for patients unable to take medications by any enteral route (e.g., in the context of severe gastrointestinal disease). In this case all components of the oral drug regimen should be stopped simultaneously, regardless of half-lives of the drugs. After resolution, all components of the antiretroviral regimen should be restarted simultaneously. [2]

A published report discussed a 78-year male with a history of human immunodeficiency virus (HIV) who received placement of a percutaneous endoscopic gastrostomy (PEG) tube during an initial inpatient visit due to a pancreatic cancer diagnosis. Due to PEG placement and the patient’s desire to continue antiretroviral therapy, the patient crushed his fixed-dose bictegravir/emtricitabine/tenofovir alafenamide under the direction of a physician. The patient maintained virologic suppression. [3]

Relevant Prescribing Information

For children unable to swallow a whole tablet, the tablet can be split and each part taken separately as long as all parts are ingested within approximately 10 minutes.

Literature Review

A search of the published medical literature revealed 3 studies investigating the researchable question:

Can biktarvy be crushed? Patient is intubated, and need to give meds through tubes. Recommendation?

Please see Tables 1-3 for your response.

Successful Bictegravir/Emtricitabine/Tenofovir Alafenamide Treatment in a HIV Patient With Swallowing Difficulties
Design	Case report
Case presentation	A 52-year-old female human immunodeficiency virus (HIV) patient who was switched to bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy®) reportedly dissolved the tablet in a tablespoonful of orange juice (with no manipulation), waited for approximately 10 minutes, and swallowed the drug. She did this on her own initiative without consulting her doctor or pharmacist. After 12 months of treatment, no problems of tolerance or adverse effects were observed. Her viral load was maintained at < 20 copies/mL over 8 months. The CD4 count improved to 370 cells/μL. By visual examination, it was observed that the Biktarvy film coating disappeared completed after 4 minutes, and the tablet was easily disintegrated in orange juice (pH 4) after 14 minutes, without agitation.
Study Author Conclusions	There are no comparative studies evaluating the pharmacokinetics of a crushed Biktarvy tablet dispersed in a liquid medium and a whole tablet. Furthermore, the current recommendations do not suggest any alternate method for Biktarvy intake apart from swallowing as a whole tablet. The results suggest that administration of the disintegrated tablet, dispersed in orange juice, could be a valid alternative in selected patients with good virological control. However, due to the lack of data on tablet manipulation, further pharmacokinetic studies are warranted to confirm this finding.

References:

Ferrández JS, García AL, Alonso-Vega GG, González AO, García TM. Successful Bictegravir/Emtricitabine/Tenofovir Alafenamide Treatment in a HIV Patient With Swallowing Difficulties. Ann Pharmacother. 2021;55(4):556-557. doi:10.1177/1060028020953631

Failure to bictegravir and development of resistance mutations in an antiretroviral-experienced patient
Design	Case Report
Case presentation	Case report of a 39-year-old woman who was antiretroviral experienced and lost to follow up presented with cerebral toxoplasmosis and was undergoing treatment. Biktarvy was started with an adequate 4-week virologic response (decreased from 1,023,292 to 1,084 copies/mL). After 2 months, the patient's condition progressed with acute neurologic deterioration, right hemiparesis, and dysphagia due to progressive multifocal leukoencephalopathy. The patient received nasogastric (NG) feeds, and Biktarvywas crushed and administered as a solution via the NG tube x 6 weeks. After 12 weeks of starting Biktarvy® therapy, the viral load was 10,232 copies/mL, and resistance testing showed several mutations (M184V, L74I, and R263K). Therapy was switched to tenofovir alafenamide, emtricitabine, and darunavir/ritonavir with only partial response (viral load 204 copies/mL).
Study Author Conclusions	In summary, after ruling out other possibilities, such as main drug-to-drug interactions, the authors believe that under-expected concentrations of bictegravir, due to an unintended misuse, are probably responsible for the virological failure and the subsequent development of resistance mutations. The authors also believe that the interest of this case relies on highlighting that although bictegravir has a high genetic barrier to resistance and high antiviral activity, standard bictegravir doses may lead to resistance development under stringent conditions, so clinicians must be aware that bictegravir cannot be used under any circumstance outside those recommended by currently available guidelines. It is not clear whether Biktarvy failure was due to past exposure with possible failure to other ARVs (lopinavir/ritonavir, tenofovir DF, emtricitabine, abacavir, raltegravir) vs. NG administration of crushed tablets.

References:

Lozano AB, Chueca N, de Salazar A, et al. Failure to bictegravir and development of resistance mutations in an antiretroviral-experienced patient. Antiviral Res. 2020;179:104717. doi:10.1016/j.antiviral.2020.104717

Crushed bictegravir/emtricitabine/tenofovir alafenamide in a human immunodeficiency virus–positive patient with esophageal cancer
Design	Case report
Case presentation	A 64-year-old white male with human immunodeficiency virus (HIV; diagnosed in 1998 with virologic suppression for 15 years) on an antiretroviral (ARV) regimen including fixed-dose combination (FDC) dolutegravir/abacavir/lamivudine presented to the clinic with a new diagnosis of esophageal adenocarcinoma with liver metastasis and significant dysphagia, causing difficulty swallowing oral medications. As the patient failed to crush the dolutegravir FDC tablet, his ARV regimen switched to bictegravir/emtricitabine/tenofovir alafenamide for smaller tablet size. A percutaneous endoscopic gastrostomy (PEG) tube was placed for enteral nutrition and he initiated chemotherapy with 5-fluorouracil and oxaliplatin. The patient returned to the infectious diseases clinic 4 months later and reported crushing his FDC bictegravir regimen with a tablet pulverizer, diluting the powder with 30 to 60 mL of water (per patient report, it dissolved easily), and then administering the medication via his PEG tube. Immediately following this daily routine, 240 mL of an enteral formula (Jevity 1.2, Abbott) was administered for a total of 1,440 mL/24 hours for nutrition requirements. A repeat HIV viral load after 4 months of crushed FDC bictegravir was undetectable (CD4 count, 371 [CD4 cells, 53%]). The patient continued on this crushed ARV regimen and his viral load continued to be undetectable after an additional 6 months. With subsequent oncolytic treatment and successful esophageal dilation, patient was able to return to oral tablet administration and nutrition.
Study Author Conclusions	In this case, the patient began crushing his ARV medication of his own volition to avoid recurrent viremia and nonadherence to his daily regimen. Successful virologic suppression was maintained after 10 months of crushed FDC bictegravir. Plasma bictegravir concentrations would have determined if adequate absorption was reliable after crushing the integrase strand transfer inhibitor, but no assay was commercially available. In this case, FDC bictegravir was successfully crushed and maintained virologic suppression. Further data are necessary to assist with the clinical applicability in similar cases.

References:

Fulco PP. Crushed bictegravir/emtricitabine/tenofovir alafenamide in a human immunodeficiency virus-positive patient with esophageal cancer. Am J Health Syst Pharm. 2020;77(7):509-510. doi:10.1093/ajhp/zxaa017