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Enteral Nutrition and Drug Administration, Interactions, and Complications

Barbara L. Magnuson, Timothy M. Clifford, Lora A. Hoskins and Andrew C. Bernard
Nutr Clin Pract 2005 20: 618
DOI: 10.1177/0115426505020006618

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Invited Review
Enteral Nutrition and Drug Administration, Interactions, and
Complications
Barbara L. Magnuson, PharmD*‡; Timothy M. Clifford, PharmD*‡; Lora A. Hoskins, RD, MS‡;
and Andrew C. Bernard, MD†‡
*University of Kentucky College of Pharmacy, †University of Kentucky College of Medicine, Division of General
Surgery, Section of Trauma and Critical Care, Critical Care Nutrition Support Team, ‡University of Kentucky
Chandler Medical Center, Lexington, Kentucky
ABSTRACT: The enteral route has become the standard
of care to deliver nutrition support for hospitalized acute
care and ambulatory care patients. The same access
device is increasingly being used to deliver medications,
which provides cost savings but also creates new chal-
lenges. Cost savings can be negated if the concomitant
administration of nutrition elicits a decrease in bioavail-
ability due to incompatibilities that alter drug or nutrition
therapy. Feeding tubes can deliver nutrients and drugs to
the stomach, small bowel, or both, with optimal efficacy of
medications depending on delivery to the appropriate
segment of the gastrointestinal tract. Liquid preparations
are often the preferred formulation for enteral adminis-
tration. Obstruction of the enteral access device may occur
when specialized medication formulations are altered
inappropriately. Occasionally, the enteral formula should
be changed to modify the content of free water, fiber,
electrolytes, or vitamins that may interfere with the drug
therapy. Intolerance to enteral nutrition such as abdomi-
nal distention and diarrhea may be the result of the
medication, and the causative agent should be identified
to improve patient comfort. This article will address
optimal drug delivery via enteral access devices and
possible complications associated with therapy.
Malnutrition is prevalent in hospitals, and the
potential for its development has led to heavy
emphasis on nutrition support.1 Parenteral nutri-
tion was historically thought to be the preferred
route. Over the last 15 years, evidence suggests the
Correspondence: Barbara L. Magnuson, PharmD, Associate Pro-
fessor, University of Kentucky College of Pharmacy, Nutrition
Support Service, Coordinator, University of Kentucky Chandler
Medical Center, 800 Rose Street, C-117, Lexington, KY 40536.
Electronic mail may be sent to blmagn0@email.uky.edu.
0884-5336/05/2006-0618$03.00/0
Nutrition in Clinical Practice 20:618–624, December 2005
Copyright © 2005 American Society for Parenteral and Enteral Nutrition
618
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enteral route for nutrition support is superior to the
parenteral route.2,3 Enteral nutrition preferentially
stimulates mesenteric blood flow, gastrointestinal
(GI) secretions, and luminal barrier protection from
opportunistic flora.4 Enteral nutrition is less expen-
sive and is much easier to manage because of fewer
fluid and electrolyte alterations. Once an enteral
route is established for nutrition delivery, drug
therapy can also be administered via this route. The
combination of enteral nutrition and drug therapy
brings about questions of bioavailability, compatibil-
ity, complications, or interactions.5 Complications
are often incorrectly attributed to intolerance of
enteral nutrition, but the cause is usually related to
the type or formulation of medication coadminis-
tered with the nutrition.6
Enteral drug administration, in this article, will
refer to providing medications through enteral
access only. This review will address only select
drug and nutrient interactions and complications
associated with administering both therapies via
enteral accesses.
Types and Uses of Enteral Access Devices
Drug interactions with enteral nutrition can cre-
ate unique challenges throughout the continuum of
care in the community, long-term, and hospital
settings, but especially in intensive or critical care.
The anatomic site of delivery and the feeding tube
size must both be considered when delivering med-
ications enterally.7 Specific nomenclature is used to
describe the site of insertion (letters O or N refer to
an orally or nasally inserted tube) and the tip
location of the feeding tube (G, D, or J refer to the
gastric, duodenal, or jejunal portions of the GI tract).
Nasoenteric feeding tubes will deliver nutrients
and medications to the prepyloric (stomach) or post-
pyloric (duodenal, jejunal) positions or both. Tubes
delivering contents only to the stomach include
nasogastric (NG) tubes and percutaneous gastrosto-
mies, whether performed endoscopically (percutane-
ous endoscopic gastrostomies: PEGs) or open (gas-
trostomies: G-tubes). Because both PEG tubes and
December 2005 EN AND DRUG ADMINISTRATION, INTERACTIONS, AND COMPLICATIONS
G-tubes are functionally the same, they will not be
differentiated and are referred to only as G-tubes in
this paper. Tubes delivering contents only to the
small bowel include nasoduodenal (ND), nasojejunal
(NJ), and jejunal (J-tubes). J-tubes, like G-tubes,
can be placed endoscopically or during traditional
“open” surgery. Although ND or NJ tubes are
intended to lie with the tip in the small bowel, they
sometimes cannot be passed into the desired posi-
tion or can be displaced from an originally satisfac-
tory position. A combination gastrostomy/jejunostomy
(PEG/J or G/J-tube) tube can deliver contents both
to the stomach and the small bowel with a single
multilumen catheter. Often the larger gastrostomy
lumen is used to remove gastric contents, whereas
the jejunal lumen is used to deliver nutrition.
Most oral medications can withstand initial
digestion in the stomach but are primarily absorbed
in the small bowel, though there are advantages and
disadvantages of delivering medications to specific
sites. Gastric tubes are usually larger in diameter
and less likely to become occluded by either medica-
tion or thick enteral formulas. The stomach is able
to tolerate more concentrated and hypertonic medi-
cations than the small bowel, making it superior to
the small bowel for drug delivery in general, and
some medications are specifically targeted for gas-
tric delivery. For example, antacids are intended to
neutralize gastric acid secretions and would provide
no benefit in the small bowel where the pancreas
secretes bicarbonate into the duodenum. Further-
more, sucralfate and bismuth are both intended to
provide a protective coating on the stomach and
would be of minimal benefit in the small bowel. On
the contrary, medication administration directly
into the stomach is contraindicated if a NG or
G-tube is in place to remove gastric secretions.
Often, medications are unavoidably removed or ren-
dered ineffective when the gastric contents are
removed by drainage or frequent suctioning.
Administering medications and nutrients into
the small bowel is usually very effective and typi-
cally well tolerated unless enteral access is too far
distal to the typical site of absorption. Many studies
report benefits of delivering nutrients into the
small bowel in critically ill or ventilated patients.8,9
Small bowel is the optimal site for delivery of en-
teral nutrition when large volumes of gastric resid-
uals are continuously removed or if a patient has
poor gastric emptying, such as that due to diabetes
mellitus or critical illness.10,11 A clear disadvantage
exists for medication delivery when a small bore
J-tube is the only enteral access available. Small-
bore J-tubes (4 – 8 Fr), may become unavoidably
clogged with medications or thick, concentrated,
fiber-containing enteral formulas. If medications
cannot be dispensed in a thin liquid formulation,
then delivery via a J-tube may need to be avoided.
When J-tube occlusion occurs, replacement is diffi-
cult and invasive. Determining alternative routes
for drug therapy in these cases is essential because
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619
tube occlusion or medication loss can prevent nutri-
tion goals from being reached, and make this route
cumbersome and less cost-effective.
Drug Bioavailability/Compatibility When
Administered With Nutrition
Changes in bioavailability often result in thera-
peutic failure of medications, as the drugs may not
be absorbed into the systemic circulation (Table 1).
Several drugs require a specific environment in the
GI tract in order to attain optimal absorption.
Examples of medications that require an acidic
medium for optimal absorption include iron and
ketoconazole. In the presence of full stomach acid,
there is increased absorption of both medications.
Absorption can be enhanced by the addition of an
acidic compound such as ascorbic acid. In the pres-
ence of hypoacidity due to a disease process or phar-
macologic intervention, these drugs have decreased
bioavailability.
Several medications should be taken on an empty
stomach, as food or enteral products reduce absorp-
tion significantly. Drugs such as ampicillin, tetra-
cycline, and loratadine have decreased absorption in
the presence of food. If these medications must be
given to a patient receiving enteral nutrition, it is
recommended that the tube feeding be interrupted
or discontinued for an hour before and 2 hours after
administration of the drug. Agents such as aledr-
onate and risendronate already have very low bio-
availabilities. The addition of food or enteral nutri-
tion will further decrease absorption and render the
agents ineffective in the systemic circulation due to
subtherapeutic concentrations.
Chelation is the binding of a divalent cation such
as calcium, magnesium, iron, or aluminum to a drug,
forming an insoluble compound. Calcium binds to
dietary phosphorus. Calcium acetate is often adminis-
tered to the end-stage renal disease population with
the intention of correcting hyperphosphatemia. This is
an unintentional interaction for the non–renal fail-
ure patient that may result in clinically significant
hypophosphatemia, particularly in the critically ill
patient.
When a drug is chelated, it is either not absorbed
or is rendered ineffective for its therapeutic intent.
A classic example of chelation is the binding of
divalent cations to the fluoroquinolone class of
antimicrobials. Ciprofloxacin bioavailability can be
reduced 27%– 67% when combined with enteral for-
mulations through this mechanism.12,13 Cohn and
colleagues12 found that even with the interaction of
ciprofloxacin with enteral feedings, the mean inhib-
itory concentrations were well above the amount
needed for clinical efficacy. Although chelation is the
most likely interaction, other mechanisms may con-
tribute to the decreased bioavailability of the fluo-
roquinolones. Therapeutic failure can be a grave
problem, particularly in the intensive care popula-
tion. Medications with narrow therapeutic indices
620
Table 1
Possible medication interactions with enteral nutrition
Know the type of enteral access device and tip location
Stomach—antacids and ketoconazole
Small bowel
Medications altering nutrients
Diuretics—decrease sodium and potassium levels and
hydration status
Steroids—alter sodium, potassium, and glucose levels
Angiotensin converting enzymes inhibitors (ACE
inhibitors)—increase potassium
Amphotericin B—decreases potassium and magnesium
levels
Calcium supplements—decrease phosphorus levels
Nutrients affecting drug therapy
Phenytoin—hold enteral feedings 1–2 hours around dose
Quinolones—decrease ciprofloxacin bioavailability with
enteral feedings
Tetracycline—chelates with divalent cations
Itraconazole—increases absorption with food
Warfarin—vitamin K, dose differs in various enteral
products
Alendronate—decreases bioavailability in presence of food
and readily available assays should be monitored.
Those medications without standardized assays to
measure plasma concentrations should be moni-
tored for clinical outcome, as opposed to therapeutic
drug concentration.
Controversy exists whether phenytoin is a drug
with dramatic changes in bioavailability when com-
bined with enteral formulas.14 Several case studies
have been published indicating that clinically signif-
icant reduction in serum levels could result in an
increased risk of seizure activity.15–17 Although the
exact mechanism of the interaction remains unclear,
there appears to be a decrease in phenytoin concen-
trations with continuous enteral nutrition, espe-
cially in hospitalized patients. It has been recom-
mended that enteral nutrition be withheld for 2
hours before and after the dose.18 Another reported
clinical practice is to modify the dosing schedule to a
twice-daily regimen and hold the enteral nutrition 1
hour before and after the dose, allowing for only 4
hours of interrupted nutrition per day.19 Phenytoin,
as with other drugs, is highly bound to albumin,
which creates an additional problem with bioavail-
ability. In cases of severe malnutrition or critical
illness with associated low albumin, the free fraction
of the drug is increased, even though total levels
may remain the same. Free phenytoin levels should
be monitored when serum albumin concentration is
⬍3 g/dL.19 A patient with these levels may have
toxic effects due to the increased free fraction of the
drug, even though the total concentration may be
within the normal therapeutic range.20 Carbamaz-
epine is another antiepileptic medication that has
an interaction with enteral nutrition. The exact
mechanism is again unknown, but the decrease in
absorption is thought to be due to the binding of the
drug to the actual feeding tube.21 Both phenytoin
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MAGNUSON ET AL Vol. 20, No. 6
and carbamazepine have narrow therapeutic indi-
ces. Any change in the absorption of these agents
can potentially increase toxicity or decrease efficacy.
Once a medication has been absorbed, there are
other nutrition factors that may affect drug therapy.
Warfarin is a common anticoagulant used for a
variety of thrombotic complications. It acts by inhib-
iting the synthesis of vitamin K– dependent clotting
factors. Therefore, consistent vitamin K intake is
crucial for maintaining therapeutic clotting times.
Attention should be paid to the enteral formulas as
they vary in the vitamin K content from 0 to 125
␮g/1000 kcal. Therefore, warfarin dosing may need
to be adjusted if the enteral nutrition support pre-
scription changes, as this could be clinically signifi-
cant. A change in vitamin K consumption from
switching enteral products may require adjusting
the warfarin dose when indicated to maintain ther-
apeutic anticoagulation. Additionally, malabsorp-
tion has been postulated as another mechanism of
decreased warfarin efficacy.22 The combination of
variable vitamin K intake along with decreased
absorption may play a large role in the decreased
efficacy of warfarin therapy in patients fed enter-
ally.
Drug and Nutrient Delivery
When administering medications concomitantly
with enteral nutrition, there are a number of tips to
keep in mind (Table 2). To prevent clogging valuable
enteral-access devices, liquid medications are the
preferred formulations. Medications should be deliv-
ered via the largest tube when multiple accesses are
available. For example, if a patient has a G-tube and
a J-tube, the G-tube is typically much larger, and
the stomach can better tolerate hypertonic medica-
tions. If the patient cannot receive medications or
nutrients into their G-tube, such as with a decom-
pression G-tube, the medications should be specially
formulated for J-tube administration. Caution
should be taken when dosing liquid medication for
adults, as manufacturers prepare many liquids in
pediatric strengths. The proper amount for an adult
should be confirmed, but if the volume is excessive,
then an alternative formulation may be preferred.
The liquid medication should be drawn up in an oral
syringe (“slip-tip” or “catheter-tip” rather than Luer
lock) to prevent inadvertent parenteral administra-
tion. If the oral syringe does not securely connect to
the feeding tube, a catheter tip adapter can be used.
When a liquid is not available, standard tablets
can be crushed or pulverized easily to form fine
powder and then dissolved or suspended in water.
To avoid a thick paste that might clog the feeding
tube, the powder should be mixed in at least 30 – 60
mL of water. Viscous liquids, such as thick syrups
and suspensions, also require dilution to avoid tube
clogging. Some liquids are too viscous, such as min-
eral oil, and may not be feasible for enteral admin-
istration. Some manufactured liquids include high
December 2005 EN AND DRUG ADMINISTRATION, INTERACTIONS, AND COMPLICATIONS
Table 2
Tips for drug administration via enteral access
Know the type of enteral access device and tip location
(stomach or small bowel).
Choose liquid medications when possible.
Administer medications through the larger enteral access
(gastric rather than jejunal).
Do not crush specialty formulation medications (EC, SR, XL,
CR, etc).
Flush feeding tube with 15–30 mL of water before and after
each drug administration.
Administer each drug separately.
Administer the entire dose of medication as a bolus.
Do not mix medications with enteral formulas.
Dilute hypertonic or viscous liquids (electrolytes) with 60–90
mL of water.
Flush feeding tube every 4 hours with 15–30 mL of water.
Teach the ambulatory patient/caregiver how to use an oral
syringe for self-medication.
CR, controlled release; EC, enteric coated; SR, sustained release; XL,
extended release.
sugar content for masking the tart drug taste, and it
may become necessary to crush tablets made for the
diabetic patient as these tablets generally do not
contain sugar. Many manufacturers now offer “sug-
ar-free” liquids as an alternative, but these may
contain large amounts of sorbitol, which may result
in diarrhea.
Mitchell and Leady23 have published a list of
medications that should not be crushed or altered.
Enteric-coated (EC) medications are intended to
prevent gastritis or acidic destruction of the drug
before absorption. Crushing EC tablets, such as
aspirin, will destroy the intended benefits of pre-
venting gastritis. Crushing of pantoprazole EC tab-
lets, for example, would allow acid to destroy the
drug before absorption. Crushing an extended-, con-
trolled-, or sustained-release (XL, CR, SR) drug
preparation could potentially result in harmful or
even fatal results. Efficacy and safety of these drugs
were determined according to their being swallowed
intact. Crushing a 24-hour release medication, such
as a SR diltiazem, would release the entire daily
dose at once, resulting in a “dose dumping” and
potential toxic effect, followed by a possible sub-
therapeutic period. Medications with special release
properties should be changed to standard formula-
tions with an equivalent daily dose.
Some capsules are filled with intact tablets, pel-
lets, or special coated granules that are also intended
to have special delayed dissolution/absorption proper-
ties. Aggrenox (Boehringer Ingelheim Pharmaceuti-
cals, Inc, Ridgefield, CT) is a capsule containing both
an intact aspirin tablet and extended-release gran-
ules of dipyridamole. This medication is often pre-
scribed in the stroke population. Ironically, these
patients often experience dysphagia from the stroke
and either have difficulty swallowing the capsule
or have a feeding tube, and crushing this formula-
tion is contraindicated. Generic aspirin-dipyridamole
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621
combinations are not currently available; therefore,
each standard-release medication should be admin-
istered separately.
The proton-pump inhibitors (PPI), such as ome-
prazole, lansoprazole, and pantoprazole, are all acid-
labile drugs destroyed by gastric acids. Crushing the
EC rabeprazole and pantoprazole will render them
ineffective when they come in contact with gastric
acid.24 The omeprazole and lansoprazole capsules
contain many EC granules to withstand the gastric
acidity. These granules dissolve and are absorbed in
the alkaline environment of the duodenum. None of
the PPIs are currently available in a premanufac-
tured liquid form. However, both omeprazole and
lansoprazole are now available in unit-dose powder
packets. The omeprazole formulation also contains
sodium bicarbonate to prevent drug degradation
from gastric acids. Both powder formulations are
intended for oral use. Intuitively, both products
could be administered via enteral access device. The
omeprazole (Zegerid, Santarus Inc, San Diego, CA)
package insert states the powder should be mixed
with 30 mL of water. The powder should not be
mixed with other liquids or food that may alter
gastric pH. The suspension should be taken on an
empty stomach 1 hour before a meal. It does not
address enteral-access administration or altering
the schedule of enteral feedings to mimic the recom-
mendation for taking on an empty stomach.25 Sev-
eral studies have shown safety and efficacy when
mixing a PPI in an alkaline bicarbonate solution for
enteral administration.26 –29 This PPI suspension
can be administered into the duodenum or stomach
and is less likely to clog the feeding tube than
attempting to suspend the intact granules in a juice.
Some medications are only available in a liquid
gel capsule. Piercing and squeezing the capsule often
produces an insufficient or inconsistent amount of
drug to obtain the intended therapeutic effect. If
another formulation is not available, consider cut-
ting the capsule in half and submersing it to allow
the liquid to dissolve. The pharmacy may have
protocols to compound large batches into liquid
syringes for better dose consistency and, more im-
portantly, safety. For example, consistency of dosing
is more critical for nimodipine, a calcium-channel
blocker used to treat subarachnoid hemorrhage, as
opposed to other gel capsules such as vitamins.
Green et al30 reported that nimodipine liquid can be
extracted from the gel capsule, stored in amber-
tinted oral syringes and a light-protected bag, and
will remain stable for up to 31 days. This practice of
batching the medication in the pharmacy improves
dose consistency and safety. Phillips et al31 reported
on medication errors, some of which were uninten-
tional administration of oral medications via the
parenteral route. By batching the oral syringes,
erroneous parenteral administration may be
avoided.
Medications should not be directly mixed with
enteral formulations. Many liquid medications are
622
acidic and will result in denaturing of the protein.
This may also lend to wastage of medications when
the formula is discarded before administering the
entire drug dose. Safety, in this practice, is of great
concern due to potential for mislabeling. The health-
care provider labeling the enteral bag may fail to
document, or incorrectly document the drug dose
added to the formula. Mixing of medication with the
formula can result in subtherapeutic effect or a
treatment failure. To avoid this, each medication
should be administered as a separate bolus to pre-
vent drug-drug incompatibilities and drug-nutrient
interactions.
Some medications should never be crushed if they
cannot be swallowed intact. Most oral chemotherapy
agents, such as methotrexate and capecitabine,
come with manufacturer guidelines for handling
and administration. Crushing a chemotherapy
agent may expose the heathcare provider to risks of
the aerosolized chemotherapy particles. Often che-
motherapy treatments are suspended until the
patient is able to swallow their medication as pre-
scribed.
Drug and Nutrient Complications
Medications are administered to elicit a specific
effect. Occasionally, medication administration is
associated with adverse events (Table 3). Enteral
formulations also have distinct properties that can
create adverse events. Changing medications or the
enteral formula can minimize these events.
Diabetes mellitus is associated with morbidity,
including cardiovascular and renal disease, de-
creased wound healing, neuropathy, etc. The
stressed patient in the intensive care unit (ICU)
may also exhibit hyperglycemia due to an acute
phase response, even if they were not diabetic before
their illness. ICU patients who are diabetic or even
nondiabetic may suffer negative effects due to
hyperglycemia. van den Berghe and colleagues32
demonstrated that strict glycemic control in the ICU
reduces mortality. Changing enteral formulas to
lower carbohydrate load or using a continuous
insulin infusion may be necessary to control hyper-
glycemia. Intermittent bolus feeding may not be
optimal due to the exaggerated swings in serum
glucose. Continuous enteral nutrition may help to
provide a more consistent carbohydrate load and
glucose levels that are therefore easier to control
with either long-acting insulin products or a contin-
uous insulin infusion.
Other nutrition alterations that may occur with
enteral drug therapy include alterations in electro-
lyte balance. Diuretics such as furosemide will
waste potassium and sodium and decrease total
body water. Supplemental potassium may be needed
to correct the hypokalemia that can be induced by
furosemide. If total body water is excessive and fluid
restriction is necessary, a more concentrated enteral
formula with lower free water content can be used.
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MAGNUSON ET AL Vol. 20, No. 6
Table 3
Common complications of medication administration and
enteral nutrition
Glucose alterations
Avoid excessive overfeeding.
Reduce carbohydrate load.
Adjust insulin to avoid hypoglycemia.
Constipation
Minimize narcotics and anticholinergic agents.
Increase free water and fiber.
Use stool softeners, stimulant laxatives, or motility agents.
Diarrhea
Eliminate sorbitol.
Reduce or dilute hypertonic medications such as
electrolytes.
Use antidiarrheal agents if Clostridium difficile toxin is
negative.
Amphotericin B is known to cause both hypokalemia
and hypomagnesemia. These electrolytes will need
to be monitored and corrected while a patient is
receiving this drug. Lithium and sodium are inter-
changeable within the renal tubule. Enteral prod-
ucts with increased sodium concentrations will
increase the elimination of lithium and therefore
decrease therapeutic levels of the drug.
Constipation and abdominal distention are com-
mon in the enterally-fed patient population and can
be causes of concern and even discontinuation of
nutrition support. Prevention strategies can reduce
them, and when present, altered bowel habits can
usually be resolved without interrupting therapy.
Constipation can result from drug therapy with
narcotics or anticholinergics. Agents such as ami-
triptyline and diphenhydramine are used frequently
and have well-documented anticholinergic effects.
Patients with disease states associated with delayed
gastric emptying may also experience constipation.
The decreased GI motility coupled with continuous
enteral nutrition can result in abdominal distention.
Aggressive bowel regimens need to be considered in
these patients to prevent distention or impaction.
Stool softeners, such as docusate, are frequently
used to prevent stool from impacting. Stimulant
laxatives, such as bisacodyl, may be used if a patient
is distended and constipated or obstipated. Metoclo-
pramide may be used for delayed gastric emptying
to prevent or treat abdominal distention. Other
modalities of preventing distention include provid-
ing more free water to the GI tract or adding a fiber
supplement. Additional free water can be obtained
by changing to less concentrated enteral formulas or
by giving free water as a bolus through the feeding
tube. Fiber promotes regular bowel movements but
also produces excess gas that can lead to distention
in many patients. Although counterintuitive, fiber
can be effective at reducing stool frequency if sup-
plemented in patients with diarrhea.33
Diarrhea in the enterally fed patient is often the
result of drug therapy. Broad-spectrum antibiotics
December 2005 EN AND DRUG ADMINISTRATION, INTERACTIONS, AND COMPLICATIONS
are often implicated as the cause of diarrhea in this
patient population, especially in the ICU. If Clos-
tridium difficile infection is suspected, it must be
diagnosed objectively with toxin assay and appropri-
ate therapy instituted before institution of other
antidiarrheal regimens; failure to eradicate the
organism and terminate toxin production may result
in toxic megacolon.34 Not all antibiotic-associated
diarrhea is C difficile–related, and simple addition
of lactobacillus to the GI tract may improve antibi-
otic associated diarrhea that is unrelated to C diffi-
cile.35 Liquid preparations of medications are also
highly implicated for causing diarrhea. Many liquid
medication formulations contain sorbitol as a sweet-
ening and dissolving agent. Sorbitol itself is a known
laxative in doses of ⬎15 g per day. Sorbitol is
considered an inert ingredient and often is not listed
in the active ingredient list in these liquid formula-
tions. The exact content of sorbitol is often difficult
to ascertain, as the excipient compounds are listed
in alphabetical order on the package. If patients
experience diarrhea while receiving these products,
consider the option of changing to tablets and crush-
ing them for enteral administration.
In addition to sorbitol, medications themselves
may be hypertonic and can cause osmotic diarrhea.
Concentrated potassium and phosphorus solutions
are both known to induce diarrhea. Magnesium
itself has strong laxative properties, such as magne-
sium citrate or hydroxide suspensions. Solubilizers
such as propylene glycol and polyethylene glycol can
cause diarrhea as well. The side effects can be
managed by diluting the preparations with water to
decrease GI irritation. With increasing osmolarity
there is increasing GI irritation. These medications
could also be changed to the tablet formulations as
well but will still require diluting the osmotic elec-
trolyte load.36
Summary
The benefits of enteral nutrition compared with
parenteral nutrition have become more evident, and
enteral use has drastically increased over the last 15
years. With this increase in enteral nutrition for
both inpatients and outpatients, a durable access
device is now frequently available for both drug and
nutrition therapy. Enteral medication delivery is
more convenient and tremendously less expensive
than medication intended for parenteral adminis-
tration. However, if medication administration
results in a clogged feeding tube or a complete loss of
enteral access due to drug and nutrient interactions
or intolerable complications, the benefits become
less evident.
Establishing enteral nutrition and drug adminis-
tration guidelines will help avoid interactions,
clogged feeding tubes, and side effects. The type and
location of the enteral access device will determine
the optimal medication therapy. Developing proto-
cols to assist healthcare providers in determining
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623
which medications to switch from the parenteral to
the enteral route will facilitate the transition and
potentially result in significant cost savings.37 Liq-
uids are the preferred formulation for enteral
administration, but many tablets can be safely
crushed and made into a liquid. If the drug therapy
cannot be enterally administered, an alternative
route should be determined, such as parenteral,
rectal, topical, buccal, or sublingual as necessary.
For optimal bioavailability, medications should
never be directly added to the enteral formulas.
Each drug should be administered separately to
avoid possible drug-drug interactions, such as che-
lation. Occasionally, it is necessary to interrupt the
enteral nutrition infusion to optimize drug efficacy.
Each medication should be diluted with adequate
water to clear the drug from the feeding tube.
Flushing the enteral access device on a schedule of
every 4, 6, or 8 hours with water or saline will assist
in maintaining the enteral access patency.
Patients, family, or caregivers should be
instructed how to properly administer the medica-
tions and flushes via the feeding tube. Outpatient
pharmacies should provide patients with oral
syringes and an adapter for their liquid formula-
tions. To avoid progression of complications, the
healthcare provider should be contacted when prob-
lems such as glucose changes, chronic diarrhea, or
severe abdominal distention occur. These practices
can improve overall patient management and result
in fewer complications as well as lower overall
healthcare costs.
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