Review Article

J Oncol Pharm Practice

0(0) 1–15
Enteral tube administration of oral ! The Author(s) 2020
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DOI: 10.1177/1078155219893449
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Samantha H Spencer , Shannon M Menard,

Malgorzata Z Labedz, Courtney D Krueger and
Katherine V Sarna

Abstract
Objective: Patients receiving oral chemotherapies face treatment interruptions if they require placement of an enteral
tube for nutrition, potentially leading to adverse outcomes in cancer treatment. Enteral tube medication administration
can provide a suitable alternative. The purpose of this review is to compile available data that describe enteral tube
administration of oral chemotherapy agents.
Data sources: A systematic evaluation of all Food and Drug Administration-approved oral chemotherapy agents
through 31 July 2019 was conducted. Information on crushing or opening of the tablet or capsule, enteral tube admin-
istration, and extemporaneous formulations was compiled from the prescribing information, tertiary resources, and
primary literature. Drug manufacturers were contacted for additional information.
Data summary: A total of 87 oral chemotherapy agents were evaluated. Of the 87 drugs, 33 agents (37.9%) had
information regarding enteral tube administration with only four drugs with nasogastric or gastric tube administration
instructions in their prescribing information. The strength of evidence varied from non-peer reviewed data to complete
evaluations of efficacy and safety. The majority of chemotherapies (62%) had no available data on enteral tube
administration.
Conclusions: The results of this review suggest that there is limited data surrounding enteral tube administration of
most oral chemotherapies, demonstrating the need for more studies to be conducted to provide more guidance to
healthcare providers when administration via an enteral tube is needed in their patients.

Keywords
Drug administration, enteral tube, nasogastric, oral chemotherapy
Date received: 28 August 2019; revised: 14 November 2019; accepted: 15 November 2019

Introduction
Oral chemotherapies have become more predominant
in the oncology and hematology treatment landscape.
In 2018, 12 of the 19 new anticancer agents approved
by the Food and Drug Administration (FDA) were
oral therapies.1 These therapies are generally preferred
by patients due to their perceived convenience.2
Unfortunately, patients receiving oral chemotherapies
can face potential treatment interruptions if they are
unable to swallow or require placement of an enteral
tube for nutrition. In these cases, nasogastric (NG) or
gastric tube administration of the chemotherapy can
provide a suitable alternative for these patients.
However, data to support this alternative route are
limited.
Further, a variety of errors have been reported with
administration of drugs through enteral tubes, and it is
essential that proper preparation and administration is
used to avoid complications.3,4 The most common
administration errors involve mixing drugs together
for administration and not flushing the tube before
and after administration of each medication, which
can lead to interactions and tube occlusion.5 Safe prac-
tice guidelines from the American Society for
Parenteral and Enteral Nutrition (ASPEN) address
medication delivery via enteral tubes; however, evi-
dence suggests clinical practice fails to adhere to these
College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
Corresponding author:
Katherine V Sarna, 833 S Wood, St Pharm 164 (MC 886), Chicago, IL
60612, USA.
Email: kzych2@uic.edu
2 Journal of Oncology Pharmacy Practice 0(0)
recommendations for medication preparation and
administration.3,6 Adherence to these ASPEN guide-
line recommendations was evaluated in a survey of
823 nurses.6 One of the major findings of the survey
included improper dilution of medications prior to
enteral tube administration. Almost all nurses reported
diluting crushed tablets or opened capsules prior to
administration; however, 72% reported using tap
water for dilution instead of the recommended sterile
or purified water (22% of respondents) or sterile saline.
In addition, many viscous liquid medications require
further dilution prior to enteral tube medication, but
only 48% of respondents reported doing so. Other con-
cerns highlighted in this survey include not separating
medication administration, failing to flush enteral tube
between medications, and administering modified-
release formulations.
In addition to limited guidance and lack of adher-
ence to best practices, most resources discuss general
consideration for medication preparation.3,4,7,8
However, these recommendations may be considered
inadequate as specific data on the efficacy, safety, and
pharmacokinetics of crushing and dissolving a medica-
tion may not be known. The purpose of this review is
to compile available information to help further sup-
port administration of oral chemotherapy agents via
the enteral tube route.
Methods
FDA-approved oral chemotherapy drugs were identi-
fied through a review of the FDA website, Clinical
Pharmacology, and the National Institute for
Occupational Safety and Health (NIOSH) hazardous
drug list.9–12 A list of drugs approved through 31 July
2019 and available in an oral preparation (tablet, cap-
sule, or liquid) was compiled. Tertiary drug resources
and prescribing information were consulted to obtain
information on crushing or opening of the tablet or
capsule, enteral tube administration, and extemporane-
ous preparation of an oral formulation; these resources
included Clinical Pharmacology, Lexicomp, the
Handbook of Drug Administration via Enteral Feeding
Tubes, and Extemporaneous Formulations for Pediatric,
Geriatric, and Special Needs Patients.11,13–15 Drug man-
ufacturers were contacted for additional information
regarding crushing or chewing of each agent, adminis-
tration via enteral tube, and extemporaneous formula-
tions. A search for relevant primary literature was
conducted in PubMed (through July 2019). All
PubMed searches combined the drug name with the
following: tube, crush, extemporaneous, solution, sus-
pension, or nasogastr*. Selection criteria of clinically
relevant articles included case reports of enteral
tube administration, pharmacokinetic analyses of
extemporaneously prepared solution or suspension,
and any extemporaneous compounding studies.
Evaluations of commercially developed liquid formula-
tions that are not yet approved were excluded from
consideration. Information from all sources was cate-
gorized based on level of evidence into on-label data,
pharmacokinetic data, case report, data on file with
manufacturer, and other (e.g. extemporaneous com-
pounding studies). When available, the type of tube
(i.e. NG, percutaneous endoscopic gastrostomy
(PEG), nasoduodenal (ND), nasojejunal) was identi-
fied. All drugs with extemporaneous formulation and/
or enteral tube administration data were further
reviewed by two authors to obtain preparation, stabil-
ity, storage, and relevant clinical information.
Results
A total of 87 oral chemotherapies were identified and
evaluated for data regarding enteral tube administra-
tion. The majority of the drugs (n ¼ 54, 62%) had no
data available to support administration through this
alternate route (Figure 1). Extemporaneous formula-
tion data were available for 14 of the 54 drugs,
though it is not known if those formulations are suit-
able for NG or gastric tube administration. Enteral
tube administration information was found for 33 of
the oral chemotherapies (Table 1). Most recommenda-
tions involved NG tube administration. Of note, alec-
tinib, ibrutinib, lenalidomide, palbociclib, and
vismodegib had data for PEG administration and a
single case report described ND administration of ima-
tinib. The level of evidence for each drug varied with
some drugs having data on oral solutions that is
extrapolated to enteral tube administration, while
others have efficacy, safety, and/or pharmacokinetic
data to support administration via this route; Table 1
denotes the level of evidence available for each drug.
Fourteen drugs (42.4%) only had non-peer reviewed
data (e.g. manufacturer data, Handbook) to support
administration. Only gefitinib, osimertinib, ruxolitinib,
and vandetanib have NG or gastric tube administra-
tion instructions in their prescribing information.52–55
Four of the 33 drugs in Table 1 have commercially
available oral liquid preparations.11 The commercially
available oral liquid formulation of larotrectinib, mer-
captopurine, and methotrexate can be given via NG or
gastric tube, but everolimus liquid formulation does
not have data describing use via enteral tube.11,56
Busulfan, cyclophosphamide, etoposide, melphalan,
methotrexate, temozolomide, and topotecan are also
formulated as injectable products, which may provide
an alternative route of administration.11
Spencer et al. 3

Abiraterone Midostaurin
Acalabrutinib Mitotane
Afatinib Neratiniba
Alpelisiba Nilotinib
Apalutamide Nilutamide
Bexarotenea Niraparib
Binimetinib Olaparib
Bosutinib Panobinostat
Brigatinib Pazopanib
Cabozantinib Pomalidomidea
Capecitabinea Ponatinib
Chlorambucila Procarbazinea
Cobimetinib Regorafenib
Dabrafenib Ribociclib
Darolutamide Rucaparib
Duvelisib Selinexor
Encorafenib Sonidegib
Enzalutamide Sorafeniba
Erdafitinib Talazoparib
Estramustine Temozolomidea
Gilteritinib Thalidomidea
Glasdegib Thioguaninea
Idelalisib Topotecan
Ixazomib Trametinib
Lapatiniba Trifluridine-tipiracil
Lomustine Venetoclax
Melphalana Vorinostata

Figure 1. Drugs with no enteral tube administration information (as of July 2019).
a
Extemporaneous formulation data available.

Discussion reliability and usefulness of the data. For example, of

A review of available literature revealed that limited
robust data exist to support administration of oral
chemotherapy via enteral feeding tubes. The type of
evidence was noted during review of the data, with
each having their own strengths and weaknesses. For
example, information from pharmacokinetic analyses
typically allowed for analysis of whether the bioavail-
ability would be disrupted with enteral tube adminis-
tration, but was typically limited on information on
how to prepare an extemporaneous formulation.
Some case reports did provide more explicit detail
on preparation and administration and provided
treatment outcomes for the individual patient; howev-
er, external validity of these types of data can be lim-
ited. Conversely, several drugs are FDA-approved
for enteral tube administration, and a few drugs have
clinical data confirming the efficacy and safety of using
extemporaneous preparations in patients with enteral
feeding tubes.52–55,57–63
When information is available, poor reporting of
preparation and administration methods challenges
the five drugs in our review where data for NG tube
administration is available (ibrutinib, imatinib, tretin-
oin, vemurafenib, vismodegib), they are supported
exclusively by case reports, which did not always pro-
vide preparation or administration instructions or
lacked detailed information on administration or
resulting outcomes.64–75 Additionally, aside from one
case report, all of the data described gastric adminis-
tration, either through an NG, PEG, or gastrostomy
tube. This limits some applicability to alternative sites
of delivery (i.e. duodenal, jejunal) as data supporting
absorption from those sites is not known.14
It is widely recognized that the oral route is the pre-
ferred method of medication administration.8,76
Therefore, while administration of medications via
enteral feeding tubes is sometimes necessary, there are
many challenges and uncertainties associated with this
practice. Incompatibles between enteral formulas and
medications administered via feeding tubes may result
in altered efficacy and tolerability of both the drugs and
enteral formula, changes to the pharmacokinetics of
 4
Table 1. Oral chemotherapy agents with enteral tube administration data.

PK Case Data Preparation and

Drug On-label data report on file Other administration Notes
16
Abemaciclib X Data on file: Crush tablet and disperse in at least Not specifically evaluated for G tube administration.16
10 mL of water; will not fully dissolve. Administer Manufacturer states that it is not expected that
within 10 min. breaking/crushing and administering via the enteric
tube route will affect the effectiveness.
Alectinib X X Data on file (water-based formulation):79 Disintegrate Two additional case reports demonstrated continued
two 150 mg capsules over 10 min in 40 mL of warm response to therapy without adverse effects.17,18 The
water. Stable for 6 h at 25 C. After administration, reports used a water-based and non-specified recipe,
flush tube with 10 mL of water three times. respectively. Both preparations were administered via
Case report (oil-based formulation):80 A 50 mg/mL NG tube, with one report utilizing a PEG tube as well.
suspension was created using 150 mg capsules with Case report that described oil-based formulation noted
olive oil NF. Ten aliquots were prepared, each con- that dissolution and clogging were encountered with
sisting of seven 150 mg capsules mixed with 10 mL the water-based solution preparation.80
of olive oil NF. All 10 aliquots were combined, and
olive oil NF added to make a final volume of 210 mL.
Stability not assessed. After administration, tube
was flushed with 30 mL of tube feeding.
Axitinib X Data on file:19 Place tablets needed for the specific Provided method was developed for clinical trial pro-
dose (for doses 2–10 mg) into a 20-mL amber-col- gram for those unable to swallow.19 Has not been
ored syringe and then add 15 mL of USP grade specifically evaluated for NG tube administration.
water. Replace plunger on the syringe, invert, and
depress plunger to expel excess air. Administer via
NG tube. Recommended to be used immediately.
Flush the feeding tube with 15 mL of water prior
and after administration.
Bicalutamide X Data on file:14 Crush the tablet to a fine powder using Data relevant to gastric administration, no specific data
a closed system (e.g. crushing syringe) and then add available on absorption from jejunal administration.
a few milliliters of water to form a paste. Add up to
15 mL of water and mix until there are no large
particles. Administer via feeding tube. Draw another
15 mL of water into the syringe to rinse and ensure
any remaining drug is delivered. Stability not
assessed. Flush the feeding tube prior and after
administration.
Busulfan X X Extemporaneous formulation:14,15 A 2 mg/mL oral sus- Extemporaneous formulation has not been specifically
pension can be prepared by crushing 120 tablets (2 mg evaluated for NG tube administration; cited as a
each) in a mortar to a fine powder. Add small amounts potential method for NG administration in the
of simple syrup to form a paste. Mix preparation as Handbook of Enteral Administration.14
you add incremental amounts of simple syrup until Pediatric PK study evaluated oral busulfan kinetics in 48
(continued)
Journal of Oncology Pharmacy Practice 0(0)
Table 1. Continued
PK Case Data Preparation and
Drug On-label data report on file Other administration Notes
Spencer et al.

sufficient quantity of almost 120 mL. Transfer prepa- patients (four received crushed tablets, two received
ration to a graduated cylinder and rinse mortar with suspensions for NG administration).20
simple syrup and add to preparation until sufficient
quantity of 120 mL. Store in an amber bottle. Stable
for 30 days under refrigeration. Flush feeding tube
after administration.
PK study:20,21 Tablets were crushed and suspended in
water. Stability not assessed.
Ceritinib X X Data on file:22 Open and empty the appropriate Protocol was developed by the manufacturer for pedi-
number of capsules into a glass bowl. Ensure that atric patients who are unable to swallow whole cap-
the capsule is completely empty. Add at least 40 mL sules or require NG tube administration and was
of water (20 mL if dose is 200 mg or less). Mix the used in a phase I clinical trial.22
ingredients carefully with a spoon. Draw up solution Additional case report available describing successful
with a syringe and administer via NG or G tube. The NG tube administration of ceritinib; method of
interior of the container used should be rinsed with administration not described, except administered
20 mL (10 mL for doses 200 mg or less) of water capsule contents.24
twice and administered to the patient. Stable for 4 h
at room temperature.
Case report:23 Patient with a NG tube was adminis-
tered ceritinib 600 mg. Capsules were opened and
powder melted with saline solution. Solution was
administered via the tube with no noted
complications.
Crizotinib X X Data on file:25 Open and empty the appropriate number Protocol for NG tube administration was developed for
of capsules into a syringe. Add one-half cup of boiling clinical studies; efficacy of NG administration not
water and one-half cup of room temperature water formally studied.
to a glass; transfer 15 mL of the mixed water to the There are an additional three case reports/series of
syringe with the capsules. Replace the plunger on the successful use of crizotinib through NG or G tube
syringe and invert continuously for 4 min to mix; (total N ¼ 5); method of administration not
then allow to sit for 10 min. Administer via the NG described.27–29
tube. Rinse the syringe with 10 mL of room tem-
perature or cold water four times. The syringe
should be inverted three times to mix for each rinse.
Administer rinses via the NG tube. Stability not
assessed. Flush the feeding tube prior and after
administration.
Case report:26 Capsules were suspended in warm
water at 50 C and then administered. No further
details provided.
5

(continued)

Table 1. Continued
PK Case Data Preparation and
Drug On-label data report on file Other administration
Cyclophosphamide X Handbook of Enteral Administration suggests that cyclo-
phosphamide solution for injection can be adminis-
tered directly via feeding tube and then flushed.14
Dacomitinib X PK study:77 A 45 mg tablet was dissolved in 1 Tbsp
(15 mL) of water in a 60 mL syringe, and then 2
Tbsp (30 mL) of Ora-Plus was added. After
administration of the dose, four 50-mL water
flushes of the G tube were given. Stability not
assessed.
Dasatinib X X X Data on file:59 Liquid suspension can be prepared for
oral administration by adding the appropriate dose
of tablets to 30 mL of 100% orange or apple juice
(without preservatives) and letting it stand. After 5,
15, and 20 min, swirl the contents for approximately
3 s. The suspension should then be administered as
soon as possible. The container should be rinsed
with 15 mL of juice and then administered to the
patient to ensure the patient receives the full dose.
Unused suspension should be discarded after
60 min.
Disintegration evaluation:30 Place a 40 mg tablet in an
oral syringe and add 5 or 10 mL tap water. Shake the
syringe for 30 s every 5 min; tablet will disintegrate
within 15 min. Stability not assessed; only feasibility
of disintegration.
Enasidenib X Data on file: Place tablet in peroxide water and allow it
to completely disintegrate and mix until homoge-
nous. (Celgene Medical Information, personal com-
munication, September 2018)
Erlotinib X X Case report:31 A 150 mg tablet was dissolved in 15 mL
of water and then administered via NG tube. No
further details provided. Therapy was stopped after
three weeks due to the development of pneuma-
tosis intestinalis.
Etoposide X X Extemporaneous formulation:35 Etoposide 10 mg/mL
solution can be prepared by diluting a desired
6
Notes
Data relevant to gastric administration, no specific data
available on absorption from jejunal administration.
Compared to historical data, Cmax and AUC are
reduced with this oral solution; clinical relevance of
this reduction is not known.77
Some pediatric clinical trials allowed for administration
of an oral suspension, and in some cases NG tube
administration, in patients who could not swallow.59
Exposure to the dispersed tablets was 36% lower
than intact tablets in pediatric patients.60 In healthy
adult subjects, dispersed tablets compared to intact
tablets had a geometric mean ratio of 0.97 for Cmax
and 0.84 for AUC.
Formal assessment of extemporaneous preparation is
not available; use via NG-route based on clinical
judgement.
There are an additional three case reports of successful
erlotinib use via NG or G tube in intubated patients in
the ICU; method of administration is not
described.32–34
A PK analysis of oral administration of an oral erlotinib
solution demonstrated similar PK parameters to the
oral tablet.78 Preparation of solution not fully
described.
Extemporaneous formulation has not been specifically
evaluated for NG tube administration; cited as a
Journal of Oncology Pharmacy Practice 0(0)
(continued)
Table 1. Continued
PK Case Data Preparation and
Drug On-label data report on file Other administration
amount of etoposide injectable solution 20 mg/mL
with sodium chloride 0.9% for injection to a final
concentration of 10 mg/mL. Store in plastic oral
syringes or amber bottle. Stable for 22 days at room
temperature.
Everolimus X Clinical trial:36,37 Phase I dose-ranging study allowed
administration of crushed tablets via G tube (3 out
of 30 patients required this route); further details on
the preparation or efficacy results in this subgroup
are not available.
Flutamide X Handbook of Enteral Administration:14 Add tablet to
syringe, then add 10 mL of water into syringe and
allow the tablet to disperse (shake if necessary).
Administer via feeding tube. Rinse the syringe with
an additional 10 mL of water and administer. Flush
tube after administration. Stability not assessed.
Gefitinib X X X Prescribing information:52 Immerse tablet in 4–8 oz of
water, stir for 15 min, and administer immediately
via NG tube. Rinse the container with 4–8 oz of
water and administer.
PK data:57 Disperse a 250 mg tablet into 50 mL of
sterile water with occasional stirring until the tablet
breaks into a fine dispersion. After administration,
give an additional 190 mL of water by the same
route of administration as the dispersion.
Case report:39 A 250 mg tablet was dissolved in hot
water (55 C) for 10 min without crushing, then
administered via G tube.
Ibrutinib X Not available.
Imatinib X Not available.
Notes
Spencer et al.
potential method for NG administration in the
Handbook of Enteral Administration (this reference
suggests more conservative 7 day BUD due to lack of
preservative).14
A PK analysis of oral administration of diluted etoposide
injectable solution demonstrated similar PK parame-
ters to historical controls for the oral capsule.61
Available commercially as a tablet for oral suspension
(Afinitor Disperz);38 has not been formally studied for
NG- or G-tube administration.37
Recommendation in Handbook based on a generic 250
mg tablet not available in the US.14 The solution was
noted to pass through an 8 Fr tube without blockage.
Data relevant to gastric administration, no specific data
available on absorption from jejunal administration.
There are an additional two case reports of successful
gefitinib use via NG or G tube; method of adminis-
tration not described.31,40
A PK study administered gefitinib tablets and extempo-
raneous solution as a drink and via NG tube in healthy
volunteers.57 The solution given via NG tube had a
mean bioavailability of 99.1% relative to the whole
tablet.
Two case reports describe successful use of ibrutinib
through an NG tube or PEG tube; method of
administration not described.64,65 One report noted
that the capsule was opened and flushed down the
feeding tube with water.65
Prescribing information provides extemporaneous
preparation instructions for patients with trouble
swallowing, but the efficacy, safety, and PK of NG
administration have not been evaluated.41,42
7
(continued)
 8
Table 1. Continued
PK Case Data Preparation and
Drug On-label data report on file Other administration Notes

Three case reports describe successful administration of

imatinib via NG tube or ND tube; method of
administration not described.66–68
Ivosidenib X Data on file:43 Place up to two 250 mg tablets in a glass Protocol for NG tube administration was developed for
bottle and fill with 20 mL of sterile water for clinical studies; efficacy of NG administration not
injection. Allow mixture to stand for 5 min. After formally studied, but the manufacturer does not
5 min, invert the bottle at least 10 times to ensure a anticipate issues with NG administration.43
uniform suspension is formed. Withdraw suspen-
sion from glass bottle in 10 mL increments, each
time inverting the bottle at least 10 times immedi-
ately before withdrawing contents. After all of the
suspension has been administered via the NG tube,
add an additional 10 mL of sterile water for injection
to glass bottle and invert the bottle 10 times;
administer contents via NG tube and continue to
rinse the bottle (at least one more time) until all
residue has been administered. Flush the NG tube
with 10 mL of sterile water before and after
administration. Recommended to be administered
within 90 min of preparation.
Larotrectinib X Commercially available as an oral solution.44 Enteral tube administration (NG or G tube) was allowed
during clinical studies.56 Food was held 1 h before and
1 h after administration.
Lenalidomide X Feasibility evaluation:45 Five 5 mg capsules were sus- Recovery of suspension after passage through PEG
pended in hot water (55 C) without grinding or tubes was assessed and no problems were noted.45
opening them for 10 min in a glass vial or syringe. Suspension can also be made with tablets.
Stable in hot water for 24 h.
Lenvatinib X Data on file:62 Place one to five capsules into a syringe. A PK analysis comparing lenvatinib plasma concentra-
Add 3 mL of water or apple juice into the syringe tions after administration of a capsule vs a suspension
with the capsules. Insert the piston and let the prepared with apple juice or water showed that both
solution sit for at least 10 min. Then shake the had similar bioavailability.62 A NG tube passing test
syringe for at least 3 min until the capsule shell is with the oral suspension was also conducted by the
dissolved and the granules are suspended. manufacturer, and no issues with tube blocking were
Administer the suspension. Rinse the syringe with observed.
2 mL of water or apple juice; shaking the syringe 10
times, then administer. Stable for 24 h when pre-
pared using water or apple juice.
Lorlatinib X Data on file:46 Place an oral tablet(s) (based on dose The PK and efficacy of NG administration have not been
desired) into an enteral syringe, replace plunger, and formally studied.46
Journal of Oncology Pharmacy Practice 0(0)

(continued)
Table 1. Continued
PK Case Data Preparation and
Drug On-label data report on file Other administration Notes
Spencer et al.

fit until just touching the tablet. Draw up water/

diluent until plunger level is at the 10-mL measure-
ment line. Invert the syringe and let it stand for
5 min. After 5 min, cap the syringe and invert a
minimum of 20 times to mix. Continue inversion if
dispersion not evenly mixed, then administer via
NG tube. Flush the NG tube with 10 mL of water
before and after administration. Stable for 3 h, but
recommended to be administered within 60 min of
preparation and not recommended to be stored.
Mercaptopurine X Handbook of Enteral Administration:14 Guidance provid- Oral suspension is commercially available in the US
ed for both the oral suspension and tablet. under the brand name, Purixan; enteral tube admin-
For suspension, administer directly via NG or G tube istration not discussed in prescribing information.47
after shaking to ensure to suspension is well-mixed.
Flush tube before and after administration.
For tablet, add tablet to syringe, then add 10 mL of
water into syringe, and allow the tablet to disperse
(shake if necessary). Administer via feeding tube.
Rinse the syringe with an additional 10 mL of water
and administer. Flush tube before and after admin-
istration. Stability not assessed.
Methotrexate X Handbook of Enteral Administration:14 Guidance provid- Recommendation in Handbook for administration of oral
ed for both the oral suspension and tablet. suspension based on a product not available in the
For suspension, administer directly via NG or G tube US.14
after shaking to ensure to suspension is well-mixed. An oral solution is commercially available in the US
Flush tube before and after administration. under the brand name, Xatmep.48 The oral solution
For tablet, add tablet to syringe, then add 10 mL of has not been evaluated for enteral tube administra-
water into syringe and allow the tablet to disperse tion, but manufacturer states that it is not expected
(shake if necessary). Administer via feeding tube. administering via this route will affect the effective-
Rinse the syringe with an additional 10 mL of water ness. (Silvergate Pharmaceuticals Medical Information,
and administer. Flush tube before and after admin- personal communication, August 2019)
istration. Stability not assessed.
Osimertinib X X X Prescribing information:53 Disperse tablet in 60 mL of A PK analysis of tablet and solution administration in
non-carbonated water. Stir solution until dispersed healthy volunteers demonstrated no difference in
(will not completely dissolve). Transfer to enteral AUC and Cmax.58
syringe and then use an additional 15 mL of water to
transfer any residues to the syringe. Administer the
30 mL solution to the NG tube. Flush tube as
(continued)
9
Table 1. Continued
10

PK Case Data Preparation and

Drug On-label data report on file Other administration Notes

appropriate (30 mL flushes). Stability not assessed;

use immediately.
Case report:49 An 80 mg tablet was suspended in
50 mL of sterile hot water for 10 min and then
administered via NG tube.
Palbociclib X Data on file:81 Add one-half cup of boiling water and NG feeding tube should be  8 Fr.81 PEG feeding tubes
one-half cup of room temperature water to a glass. with a diameter between 12 and 28 Fr are suitable.
Place capsule into a 20-mL syringe and then add Recommended to be administered immediately after
15 mL of mixed water. Place the plunger into the a patient’s nutritional supplement.
syringe and press until the plunger is at the 20-mL
mark (syringe cap will need to be loosened to expel
air during this process). Shake vigorously up and
down continuously for at least 4 min and then allow
to sit for 10 min. Gently invert several times to
ensure suspension is well-mixed and then adminis-
ter via NG or PEG tube. Rinse the syringe with
10 mL of water five times, administering each rinse
via NG or PEG tube (trace amount of capsule shell
may still remain in syringe). Flush tube before and
after administration with 10 mL of water. Stable for
2 h at room temperature when stored in the
syringe.
Ruxolitinib X Prescribing information:54 Add tablet to 40 mL of NG feeding tube should be 8 Fr.54
water and stir for 10 min to suspend. Administer via
NG tube. Rinse tube with approximately 75 mL of
water. Recommended to be administered within 6 h
of preparation.
Sunitinib X Data on file:63 Empty contents of the capsule into a Protocol for G-tube administration was developed for
container. Add 5 mL of normal saline and swirl for clinical studies; potency of the capsules was retained
60 s to blend. Attach barrel of a syringe to G-tube using the manufacturer’s method.63
connector and then pour suspension into the
syringe to administer. Rinse the container with 5 mL
of normal saline twice, administering each rinse via
G tube. Flush syringe and tube with 5 mL of water
twice after rinses. Administer as soon as possible
(within 15 min).
Tretinoin X Case report 1:69 Capsule was placed in 50 mL tube Several case reports of tretinoin NG administration are
with 20 mL sterile water. The tube was heated in a available; all have limitations in using methods that
water bath at 37 C to melt the capsule. The oily may not accurately obtain all of the contents of the
Journal of Oncology Pharmacy Practice 0(0)

(continued)
Table 1. Continued
PK Case Data Preparation and
Spencer et al.

Drug On-label data report on file Other administration Notes

suspension was administered via NG tube to two tretinoin capsule and that may not adequately protect
patients. staff preparing the dose.21,50
Case report 2:70 Capsules were opened and partially
aspirated into a glass syringe. Remaining contents of
the capsule were then mixed with soybean oil and
aspirated into the same syringe. The mixture was
administered via NG tube to one patient.
Case report 3:71 Capsules were softened by placing
them in warm milk (37 C). Once softened (about
2–3 min), contents were drawn out of the capsule
with a syringe and administered via NG or G tube.
Case 4:72 Liquid from capsules (method for removal
not discussed) was administered to two patients via
a feeding tube. Low plasma levels were detected
after administration with this method.
Vandetanib X Prescribing information:55 Dissolve tablets in 2 oz of
water. Stir solution for 10 min; all contents will not
dissolve. Administer via NG or G tube. Rinse con-
tainer with 4 oz of water and administer.
Recommended to be administered immediately.
Vemurafenib X Case report 1:73 Capsule was dissolved in 15 mL of Vemurafenib is almost insoluble in water, but the tablets
water, and the cellulose precipitate was removed are formulated as a microprecipitated bulk powder
after dissolution. The solution was administered via that increases solubility.51
NG tube to one patient. The NG tube was flushed
with 30 mL of water per every capsule given; addi-
tional tube feeds were held for at least 60 min after
administration.
Case report 2:74 Capsule was crushed in solution and
given via NG tube to one patient. No further details
on administration were available.
Vismodegib X Case report:75 Capsule was diluted in 50 mL of warm
water and administered via PEG tube with no noted
complications.
AUC, area under the curve; BUD, beyond use date; Cmax, maximum serum concentration; G tube, gastrostomy tube; ICU, intensive care unit; ND, nasoduodenal; NF, National Formulary; NG, nasogastric;
PEG, percutaneous endoscopic gastrostomy; PK, pharmacokinetic; USP, United States Pharmacopeia.
11
12
the drug, and tube occlusion; these issues are well char-
acterized across tertiary resources.3,8,14 In our review,
holding tube feeds around the time of drug administra-
tion was recommended for three drugs (larotrectinib,
palbociclib, and vemurafenib), but was otherwise not
specified. Pharmacokinetic analyses comparing extem-
poraneously prepared and commercially available
preparations found decreased bioavailability for for-
mulations containing dacomitinib and dasatinib and
no differences for those containing erlotinib, etoposide,
gefitinib, lenvatinib, and osimertinib.57,58,60–62,77,78
Last, to prevent tube occlusion, several reports recom-
mend the use of a specific preparation (e.g. oil vs.
water-based formulation of alectinib) or tube
size (size 8 Fr or greater for flutamide, palbociclib,
and ruxolitinib preparations) to circumvent this
issue.14,54,79–81 For the latter concern, ASPEN does rec-
ommend tubes with an internal diameter  10 Fr for
administering crushed or dissolved solid dosage medi-
cations; for smaller diameters, only liquid formula-
tions, with few residuals, should be used.3
Although there is variable and limited evidence for
enteral tube administration of many oral chemother-
apy agents, there are some general parameters to
help promote safe and effective medication adminis-
tration via enteral tube. The ASPEN provides
detailed guidance on safe preparation and adminis-
tration of medications through enteral feeding tubes.3
Although a thorough discussion is beyond the scope
of this review, a few key points are applicable.
Medications should not generally be mixed with
enteral formulas or with other medications. Such
admixtures could result in incompatibilities that
create tube obstruction or alter efficacy of the med-
ication as noted above. At least 15 mL of water
should be used to flush the tube prior to and follow-
ing medication administration unless prohibited by
fluid restriction. When no specific recommendations
are available for diluting powdered medication,
ASPEN recommends a dilution with 30–60 mL of
purified water. Injectable formulations of medications
may be suitable for enteral tube administration as
well, but absorption can be impacted by the salt
form, oral bioavailability, and pH.3,14
In addition, because of the hazardous nature of the
drugs included in this review, safe handling is para-
mount. Publications from the American Society of
Health-System Pharmacists, NIOSH, and Occupational
Safety and Health Administration, as well as United
States Pharmacopeia <800>, may be consulted for
detailed information on safe handling and administra-
tion of hazardous drugs.12,82–84 Briefly, wearing personal
protective equipment, double gowning, using closed
system transfer devices, and working within certified bio-
logical safety cabinets can help reduce occupational
Journal of Oncology Pharmacy Practice 0(0)
exposure risk. Reproductive risks associated with han-
dling hazardous drugs should also be considered, and
affected individuals should be offered alterative work
assignments.85
This study has a few limitations. First, the search
strategy did not encompass primary literature pre-
sented solely at congresses. Though these data are lim-
ited in data presented (i.e. abstract only), some
additional case reports or other supporting data may
have not been identified. Additionally, as only PubMed
was selected to locate articles, full text publications
published in journals indexed outside of this secondary
database would have been missed. Last, some of these
drugs have not been on the market long enough to have
post-marketing and pharmacokinetic data available to
support this route of administration.
Overall, while inappropriate administration of
medications via enteral feeding tubes may lead to
adverse events, there is even greater concern for with-
holding lifesaving therapy from patients with other-
wise limited treatment options.86 The information
presented in this review is intended to be used by
clinicians as a guide, along with clinical judgment,
for determining potential techniques for preparing
and administering oral chemotherapy via enteral feed-
ing tubes. The availability of extemporaneous prepa-
rations data not covered in this review, along with
careful clinical judgment, may also generate additional
opportunities for administration of oral chemotherapy
via this route.
Conclusion
Data supporting the administration of oral chemother-
apy via enteral feeding tubes are limited and challenged
by inconsistent and incomplete reporting of key com-
ponents of the medication preparation and administra-
tion process. When drug-specific data are available,
these methods should be utilized over general medica-
tion preparation and administration recommendations.
When data are not available, clinicians should use a
multidisciplinary approach incorporating general prin-
ciples of enteral tube medication administration to
improve the safety for both patients and healthcare
providers.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest
with respect to the research, authorship, and/or publication
of this article.
Funding
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
Spencer et al.
ORCID iD
Samantha H Spencer https://orcid.org/0000-0002-8496-
3554
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