Clinical Nutrition (2001) 20(2): 187–193

& 2001 Harcourt Publishers Ltd

doi:10.1054/clnu.2000.0155, available online at http://www.idealibrary.com on

EDUCATIONAL PAPER

Enteral feeding: Drug/nutrient interaction

R. LOURENC°O
Pharmacy Department, Centre of Nutrition and Metabolism, University Hospital Sta. Maria, Lisbon, Portugal (Correspondence to:
R L, Dept of Pharmacy, University Hospital Sta. Maria, Av. Prof. Egas Moniz, 1649-035 Lisbon, Portugal)

AbstractöEnteral nutrition support via a feeding tube is the ¢rst choice for arti¢cial nutrition. Most patients also require
simultaneous drug therapy, with the potential risk for drug^nutrient interactions which may become relevant in clinical
practice. During enteral nutrition, drug^nutrient interactions are more likely to occur than in patients fed orally. However,
there is a lack of awareness about its clinical signi¢cance, which should be recognised and prevented in order to optimise
nutritional and pharmacological therapeutic goals of safety and e⁄cacy.
Learning objectives:
. To raise the awareness of potential drug^nutrient interactions and in£uence on clinical outcomes.
. To identify factors that can promote drug^nutrient interactions and contribute to nutrition and/or therapeutic failure.
. To be aware of di¡erent types of drug^nutrient interactions.
. To understand complex underlying mechanisms responsible for drug^nutrient interactions.
. To learn basic rules for the administration of medications during tube-feeding. & 2001Harcourt Publishers Ltd.

Key words: enteral feeding; drugs; nutrients; interac-
tions; pharmacokinetics
Introduction
Dietary manipulations have raised concerns related to
the impact of nutrition support and nutrition formula
composition on the pharmacological activity of drugs
(1). In clinical practice, particularly during tube-feeding,
drug–nutrient interactions (DNI) may influence out-
comes (2). The role of the pharmacist in the nutrition
support team is paramount for its recognition and
prevention; often patient management involves simulta-
neous administration of enteral feeding and drug
therapy (2, 3). The potential risk of DNI can compro-
mise both nutritional and pharmacological therapeutic
goals of safety, efficacy and quality of care (4). This
paper provides a general and brief overview of different
aspects to be taken into consideration in everyday
practice, mainly for patients in hospital where drug
regimens may be changed quite often.
Definition of drug-nutrient interactions and consequences
A DNI can be defined as 1. the modification of the
effects of nutrients by the prior or concurrent adminis-
tration of a drug or 2. the modification of the effects of
one drug by the prior or concurrent administration of
nutrients (Table 1). Important clinical outcomes can
ensue, including modifications of nutrition support
efficacy and/or drug pharmacological response (1). A
broad range of effects and degrees of expression can
occur. Sometimes, there is some benefit; e.g. nifedipine
absorption is delayed when the drug is taken with food,
which reduces drug-related flushing and increases
patient compliance to treatment (1). However, enhanced
absorption of certain drugs (hydrochlorothiazide, dia-
zepam, propranolol, griseofulvin) is observed when they
are administered simultaneously with food, leading to a
consequent increase in the drug bio-availability which
may be beneficial or detrimental (5). The term ‘inter-
action’ is usually associated with patient outcomes of
potential clinical relevance (Table 1). DNI may induce
either nutrition support inefficacy or unwarranted
pharmacological response (1). Concurrent drug admin-
istration may lead to a deficient intake or reduced
absorption of nutrients. Anorectic drugs reduce food
intake (1, 6). Cytotoxic drugs are commonly associated
with nausea, vomiting and taste disturbances which may
affect nutrient intake and/or absorption, often com-
pounded by electrolyte or trace element losses (1, 6).
Drugs that act on the gastrointestinal (GI) tract, such as
prokinetics, histamine H2 antagonists and antacids may
worsen diarrhoea (1, 7–9). Antacids can promote the
loss of integrity of various components of the enteral
formula such as changes in texture, viscosity or physical
form that may clog the feeding tube (8–10). Thus, the
administration of antacids and enteral feeds must be
separated by a 2 h interval.
Alternatively, DNI may result in reduction, toxicity
or even complete failure of drug therapy, although the

187
188 ENTERAL FEEDING: DRUG/NUTRIENT INTERACTION
latter is rare (11). Subtherapeutic drug blood levels
(Table 1) have been observed when digoxin is taken with
a diet enriched in fibre, especially pectin (1, 11). Several
reports support an interaction between phenytoin
suspension and enteral feeding leading to a reduced
phenytoin absorption and therapeutic effect (1, 8, 9).
Although the specific mechanism has not been estab-
lished, the reduced GI absorption of the drug appears to
be related to the formation of either phenytoin-calcium
or phenytoin-protein complexes. Furthermore the acidic
properties of the enteral formula may alter the solubility
of phenytoin with a reduction in phenytoin bioavail-
ability. A different interaction has been suggested for
Warfarin, which may bind to the protein source of the
enteral formula resulting in decreased drug levels (8, 9,
12, 13). The possible interaction between diet compo-
nents and drugs with a narrow therapeutic index (e.g.
anticoagulants) enhances the likelihood of their toxicity.
Large doses of vitamin E (greater than 400 IU) can
potentiate the effects of anticoagulants enhancing
bleeding risk (6). Fish oil contains o-3 fatty acids, which
may enhance anticoagulation (6, 13). On the contrary,
dietary vitamin K tends to antagonise the anticoagulant
effect of Warfarin (8, 9, 12, 13).
Factors influencing drug-nutrient interactions
The magnitude and incidence of DNI is related to a
large inter- and intra-patient variability (5, 6). Indeed, it
is difficult to predict with accuracy what will happen
when an individual patient is given simultaneous enteral
nutrition and drugs. Key factors are shown on Table 2,
and include patient profile, nutrition regimen dependent
variables and drug characteristics (5, 14).
Patient profile
The risk of interaction depends mostly on the char-
acteristics of the exposed individual, including age,
Table 1 Drug-nutrient interactions
1. Drug induced
Deficient intake/reduced absorption of nutrients: e.g. anoretic, cytotoxic,
prokinetic drugs, histamine H2 antagonists, antacids
Loss of integrity of enteral formula: e.g. antacids
2. Nutrition induced
Subtherapeutic drug blood levels: e.g. digoxin, phenytoin, warfarin
Toxicity: e.g. anticoagulants
Table 2 Drug-nutrient interactions: key factors
Patient Nutrition regimen Drug
Age Placement of Therapeutic
feeding tube index
Nutritional status Formula characteristics Dose-response
curve
Disease: Feeding tube Potency
organ (s) involved Delivery methods
acute, chronic, severity Maintenance protocols
nutrition and disease status (1). Infants, children and the
elderly are at increased risk (6, 11). Both the young and
the elderly have an inefficiency of drug metabolising
enzymes, an often disturbed renal function and a narrow
gap between drugs’ therapeutic and toxic levels (1, 6). In
addition, the elderly often consume poor/restricted
diets, either by prescription or choice, and are frequently
on long-term polymedication (1, 6, 11). Both obesity
and undernutrition can alter the pharmacokinetic of
drugs (4). The latter may be associated with a loss of
absorptive capacity of the intestine, a fall in plasma
albumin and a reduced activity of the drug metabolising
enzymes–all predisposing to DNI (5, 6, 11). Concomi-
tant disease states, such as renal or hepatic failure
influence pharmacokinetics (4). The risk of DNI is also
greater in patients who have increased or specific
nutritional needs (e.g. burn/cancer patients), as well as
in the presence of certain chronic diseases which require
various medications; e.g. hypertension, cardiac failure,
diabetes mellitus (11). Physiological states, such as
pregnancy and lactation are of special concern because
of possible repercussions in the offspring.
Nutrition regimen
Enteral feeding can be provided to patients for complete
sustenance or as a supplement; the type of enteral
formulae and the delivery process are key factors to its
success (Table 2) (15).
Tube feeding placement: The bioavailability of drugs,
whose absorption is pH dependent, can be affected by
tube feeding placement, and is dependent on whether the
distal tip is in the stomach or small intestine (8).
Hypertonic and hyperosmolar preparations, either as
drugs or enteral formulae, must be administered into the
stomach to avoid GI intolerance (12).
Formula characteristics: The composition of enteral
formulae is complex and contains different substrates,
which can interact with each other and/or with certain
drugs enhancing the risk of nutrition and drug therapy
failure (10). Feeding-tube occlusion is considered a
major complication of enteral feeding and is influenced
by several factors, including the protein source of the
formula (9, 16, 17). Formulae containing intact protein,
particularly casein or caseinates, and higher protein
concentrations, are more prone to coagulate, thereby
clumping into the feeding-tube, in particular when
exposed to an acidic pH, a feature of some pharmaceu-
tical syrups (9, 16, 17).
Feeding tube: The available feeding-tubes are diverse:
in composition of the material, inner diameter, length,
number and location of delivery holes at the distal tip,
and the number of delivery ports (10, 16, 17). Though
less patient friendly, large-bore nasogastric tubes appear
less likely to occlude than smaller diameter tubes and/or
tubes with multiple small delivery holes (10).
Delivery methods: The method of enteral feeding
delivery also contributes to feeding-tube occlusion.

Continuous gravity feeding results in a greater incidence
of tube occlusion compared with intermittent gravity
feeding, presumably related to the frequent flushing with
water between the feeding intervals (16, 18). Though
pump-assisted tube-feeding is more prone to success,
pump malfunction is associated with irregularities on
the rate of feeding delivery and consequently increases
the potential for occlusion (16).
Maintenance protocols: Flushing the tube with water
before and after drug administration is an effective way
of preventing occlusion and helps to prevent DNI. In
addition, water provides an excellent medium to deliver
medication, enhances its absorption and optimises
enteral tube patency (12, 16, 19).
Drugs: The probability of DNI is also determined by
the drug itself (11). In general, high-risk drug are those
with a narrow therapeutic index, such as theophylline,
phenytoin and digoxin (6). Others, have a steep dose-
response curve, thereby a small increment in dosage
induces a large increase in therapeutic effects, as seen
with corticosteroids, rifampin and carbamazepin. Ad-
ditionally, drugs with potent pharmacological effects,
such as anti-coagulants, also increase the risk of DNI (6).
Types of drug-nutrient interactions
DNI are frequently typified as pharmacokinetic or
pharmacodynamic (Table 3) (1, 5). Pharmacokinetic
interactions influence the disposition of a drug or nutrient
in the body and involve effects on absorption, distribu-
tion, metabolism and excretion. Pharmacodynamic inter-
actions are related to the pharmacological activity: their
consequences range from insignificant, or no clinical
effect, to significant morbidity and even mortality.
Pharmacokinetic interactions
(a) ABSORPTION. Although interrelated with bioa-
vailability, is a different and major issue. Absorption
involves the transport of the drug or nutrient from the
GI tract into the general circulation; bioavailability is
the percentage of the original dosage, which, with or
without further metabolism, reaches the systemic
circulation as an active moiety (12). Absorption is
undoubtedly the best-studied and most common para-
meter responsible for pharmacokinetic interactions.
Disturbances in drug or nutrient absorption more often
result in reduced absorption of either one (1, 20),
moreover an alteration in the absorption rate tends to be
less important than changes in the total amount
absorbed (6, 8, 11). However, interactions that affect
the absorption rate of drugs are mainly relevant for
those with a short half-life or when a rapid peak plasma
level is required to achieve a therapeutic effect (1).
Mechanisms involved in DNI that affect absorption
are shown in Table 4 (1, 3, 5, 11, 12). In general,
physicochemical incompatibilities and interference with
CLINICAL NUTRITION 189
GI pH are associated with the formation of therapeu-
tically inactive products. On the other hand, GI motility,
secretions and flora as well as mucosal morphology and
function are more likely to induce changes in the
absorption rate.
Physicochemical incompatibilities: Adsorption is a
physical process whereby a drug is bound to an external
component, either from the diet or the tube, thus
decreasing its bioavailability. Adsorption appears to be
mainly related to the fiber content (Table 4). Dietary
fibre increases the absorption rate of amoxicillin but
significantly decreases the amount of drug absorbed,
possibly due to adsorption of amoxicillin to the fibre
matrix (5). High pectin diets act as an adsorbent to
paracetamol (11). Both pectin and oat-bran fibre reduce
the absorption of lovastatin (21). In all instances, it is
advisable to separate feeding and medication intake,
ideally with a 2 h interval.
Complexation is a different mechanism. Dietary
minerals - zinc, iron, calcium, and magnesium-form
insoluble complexes with tetracycline, quinolones and
antacids (1, 11). The use of antacids containing alumi-
nium and magnesium can, occasionally, cause clinically
significant phosphate depletion by the formation of
insoluble aluminium or magnesium phosphates (1, 13).
The chelation of levodopa by iron can reduce Parkin-
son’s disease control (6). Sucralfate binds to protein
components of the diet, causing insoluble complexes
(bezoar formation) and consequently therapeutic ineffi-
cacy (12). All these drugs should be taken with an empty
stomach, at least 1 h before each meal.
Disruption of integrity of the enteral formula may
result from its mixture with syrups or suspensions
buffered to pH  4. As a consequence enteral products
increase their viscosity, particle size and thickness,
thereby causing cause immediate clumping, as described
above in the section ‘Factors influencing drug-nutrient
interactions’ (3).
Table 3 Types of drug-nutrient interactions
Pharmacokinetic interactions
(a) Absorption
Physicochemical incompatibilities
Gastrointestinal pH, motility, secretion and flora
Mucosal morphology and function
(b) Distribution
Protein binding (e.g. high fat or low protein diet)
(c) Metabolism
Formulae composition
Drug metabolic pattern (e.g. theophylline)
Macronutrient and electrolyte homeostasis (e.g. corticosteroids,
cyclosporine, diuretics)
Vitamin metabolism (e.g. isoniazid vs pyridoxine; phenytoin vs folic
acid/vitamin D; methotrexate/phenobarbitone vs folic acid; furosemide
vs thiamine; cimetidine/ranitidine/omeprazole vs cianocobalamine)
(d) Excretion
Urinary pH: alkaline pH (e.g. nitrofurantoin, allopurinol); acidic pH
(e.g. amitriptylline)
Pharmacodynamic interactions
Pharmacologic activity
Antagonism (e.g. warfarin)
Cellular transport system (e.g. levodopa)
190 ENTERAL FEEDING: DRUG/NUTRIENT INTERACTION
Table 4 Drug-nutrient interaction: mechanisms that affect absorption
Physicochemical incompatibilities
Adsorption: e.g. fibre/pectin vs amoxicillin/paracetamol/lovastatin
Complexation: e.g. dietary minerals vs tetracycline, quinolones,
antacids; phosphate vs antacids; levodopa vs iron, sucralfate vs protein
Distruption of enteral formula: drugs with pH  4
Gastrointestinal pH
: absorption with acidic pH milieu: e.g. thiamine, cyanocobalamine,
iron, isoniazid, sucralfate, ketoconazole
: absorption with alkaline pH milieu: e.g. ciprofloxacin, omeprazole,
didanosine
Gastrointestinal motility
Diseases/surgical interventions
Diet: e.g. consistency, postprandial conditions, composition
Drugs
(1) Mechanism of action
; gut motility (e.g. atropine, antihistamines, tricyclic antidepressants,
sympathomimetics, anaesthetic, antacids with aluminium)
: gut motility (e.g. prokinetics, erythromicin, bisacodyl, senna,
lactulose, neostigmine)
: gastric acid secretion (e.g. reserpine)
(2) Osmolarity concentration (e.g. formulation type, sorbitol as
excipient)
Gastrointestinal secretions
Pancreatic enzymes, bile salts: e.g. griseofulvin, atovaquona
Gastrointestinal flora
Clinical conditions, drugs (e.g. antibiotics, histamine H2 inhibitors,
proton pump inhibitors)
Mucosal morphology and function
Clinical conditions, drugs (e.g. non steroidal anti-inflammatory agents)
Gastrointestinal pH: Alterations in pH influence both
the ionized and nonionized form of the drug or nutrient,
thereby influencing the absorption process (11). Thia-
mine, cyanocobalamine and iron absorption are com-
promised when drugs that increase gastric pH (antacids,
histamine H2 antagonists and proton pump inhibitors)
are administered simultaneously (6, 22). On the other
hand, the sustained presence of nutrients in the stomach
increases gastric pH thereby preventing the dissolution
and absorption of isoniazid (11). Sucralfate needs an
acid milieu to become active in order to have a
therapeutic effect (12). Ketoconazole requires an acidic
environment to ensure proper dissolution and absorp-
tion (9, 12, 15, 23). On the contrary, ciprofloxacin and
omeprazole have improved absorption when adminis-
tered at an alkaline rather than an acidic pH.
Didanosine (a purine nucleoside analogue with anti-
HIV activity) requires protection against acid catalysed
decomposition. Nutrients in the stomach enhance the
amount of didanosine absorbed but have no effect on
the rate of absorption (21). In summary, the influence of
GI pH is debatable, and its change, either natural or
induced, should initiate a careful search of known
interactions in order to avoid them.
Gastrointestinal motility: Gut motility, including gas-
tric emptying rate (GER) and intestinal peristalsis,
determines the absorption rate for drugs and nutrients
and the onset of their pharmacological activity through
various mechanisms (Table 4) (1, 8, 15).
GER is delayed by some clinical conditions (including
malnutrition, head and/or severe trauma, myocardial
infarction, appendicitis, pancreatitis, atrophic gastritis,
diabetic gastroparesis and pyloric stenosis) as well as
surgical interventions (laparotomy and vagotomy)
(1, 8, 15).
The type of diet influences gut motility. Fluid diets
speed up GER whereas postprandial conditions delay
GER. Moreover, highly concentrated formulae in
macronutrients, mainly amino acids and fat enhance
this delay (6, 8, 11).
Drugs may influence gut motility through their
mechanism of action (by acting on the GI smooth
muscle or stimulating the release of intestinal hormones
that control GI activity) or by the osmolarity of the drug
formulation (8). Atropine, scopolamine, phenothiazine,
antihistamines and tricyclic antidepressants can inhibit
GER and GI motility (8, 12, 24). Sympathomimetics
(dopamine and dobutamine) reduce splanchnic blood
flow, promote smooth muscle relaxation and decrease
GI contractions (8, 12, 15). Anaesthetic agents and
opiate agonists have similar effects on the GI tract
(8, 12, 24). Aluminium, a constituent of many antacids,
produces a relaxing effect on gastric smooth muscle,
which leads to a delayed GER (8, 11, 12). On the
contrary, prokinetic agents (cisapride, metoclopramide,
and domperidone) enhance GER and the contractility of
the intestine (7, 8, 12, 24). The macrolide erythromycin,
which acts primarily as a motilin receptor agonist on the
GI smooth muscle, also induces an augmented peristal-
sis (26). Bisacodyl and senna (stimulant laxatives)
produce GI irritation leading to depletion of minerals,
while lactulose causes diarrhoea (6, 8). Neostigmine
increases intestinal tone. Reserpine increases GER by
stimulating gastric acid secretion (8, 15). The osmolarity
of the drug formulation determines the nonpharmaco-
logic actions of a medication, which modifies the
tolerance to enteral feeding (Table 4). Diarrhoea,
bloating and cramping are common and may be the
end result of drugs with a high osmolarity (electrolyte
solutions, syrups, certain suspensions) or containing
large amounts of sorbitol (8, 9, 12, 15). Sorbitol is an
inert excipient often used in liquid formulations to
enhance palatability and improve stability. However, it
also increases their osmolar concentration; thus the
severity of intolerance is related to the amount of
sorbitol. Doses as low as 10 g are known to cause mild
GI distress while 20 g or more promote more severe
symptoms. Children may be more susceptible to sorbitol
than adults (12, 15).
Gastrointestinal secretions: The presence of nutrients
in the GI tract, especially a large quantity of fat,
stimulates secretion of pancreatic and bile secretions.
Pancreatic enzymes have a limited role in drug absorp-
tion whilst bile may have a more significant effect (Table
4). Bile salts are surface-active agents and can increase
the dissolution of lipossoluble drugs with consequent
enhanced absorption: e.g. griseofulvin and atovaquona
(6). Bile salts may promote the formation of nonabsorb-
able precipitates (e.g. neomycin); sterol excretion is then
increased, thereby reducing the body’s cholesterol pool
(13).

Gastrointestinal flora: Besides gastric intolerance,
broad-spectrum antibiotic administration may reduce
or alter small intestinal and colonic bacteria (Table 4),
thus promoting diarrhoea and nutrient availability, e.g.
vitamin K (1, 9, 13). Bacterial overgrowth of the
proximal gut, whether spontaneous or induced omepra-
zole, appears to lead to the synthesis of folic acid (25)
and vitamin K (26).
Mucosal morphology and function: Drugs may affect
mucosal integrity (Table 4). Nonsteroidal anti-inflam-
matory drugs may even cause bleeding from the GI
tract. Neomycin and colchicine may induce enteropathy,
which interferes with active transport mechanisms for
nutrients (1, 6, 13).
(b) DISTRIBUTION of a drug or nutrient is another
type of DNI which may be disturbed by competition for
binding to transport proteins (Table 3). In theory, an
enriched fat diet increases the plasma free fatty acids
that transiently displace drugs bound to albumin, with a
possible exacerbation of the pharmacological effect of
the drug (5) although no clinical relevant examples have
been reported. A prolonged relative deficiency of protein
intake may decrease plasma albumin and as such may
influence the disposition of drugs, whenever the effect is
related to the albumin bound moiety (5, 13).
(c) METABOLISM (Table 3) is influenced by the diet
composition as well as by the drugs’ metabolic pattern
(1). Because nutrients interfere in the synthesis and
activity of metabolising enzymes, the concurrent admin-
istration of drugs and nutrients can interact in a way
which may affect the activity of both or either one
(1, 14). This is usually associated with the stimulation or
inhibition of metabolising enzymes or derives from
changes induced in splanchnic-hepatic blood flow (14).
As an example of the former mechanisms, theophylline
half-life significantly decreases in patients fed with high
protein or low carbohydrate diets (3, 5, 14, 15); whereas
the concurrent intake of a high fat meal has been
associated with signs of drug toxicity (1). However,
dietary protein and fat stimulate splanchnic-hepatic
blood flow, which is relevant for drugs with high hepatic
extraction ratios, such as propranolol and labetalo
(1, 11, 14).
Furthermore, certain drugs alter the metabolism of
macro and micronutrients (1, 8, 9). Protein and glucose
metabolism is influenced by corticosteroids, while
cyclosporine affects lipid metabolism (6, 13, 27).
Diuretics as well as amphotericin B, captopril and
cisplatin are responsible for electrolyte disturbances
(6, 11). Some drugs interact with vitamin metabolism,
e.g. isoniazid affects pyridoxine; phenytoin may interfere
with folic acid and vitamin D; phenobarbitone, primi-
done, sulphasalazine, trimethoprim and methotrexate
(in high doses) antagonise folic acid (1, 11). Long-term
furosemide therapy may increase urinary loss of
thiamine, thereby contributing to impaired cardiac
CLINICAL NUTRITION 191
performance in patients with congestive heart failure
(28). Prolonged or chronic therapy with cimetidine,
ranitidine and proton pump inhibitors, by inhibiting
gastric acid secretion, may promote malabsorption of
cyanocobalamine, which can increase the risk of
anaemia, particularly in the elderly (1, 22).
(d) EXCRETION (Table 3). Both diet and drugs can
cause alkaline or acidic urine (1). Low protein diets lead
to increased urinary pH. The alkalinization of the urine
increases the excretion of nitrofurantoin and its effec-
tiveness. Additionally, nitrofurantoin tolerance and
absorption is enhanced when it is taken with food
(29). Low protein diets may increase renal reabsorption
of quinidine, alongside the risk of drug toxicity. Similar
diets also promote the renal tubular reabsorption of the
allopurinol main metabolite (oxypurinol), leading to
toxicity with important practical implications in the
elderly (1). On the contrary, a high protein diet
determines an acidic urine which increase the rate of
excretion of cationic drugs such as amitriptylline. A high
protein diet also increases renal plasma flow and
glomerular filtration rate mediated by glucagon release
(1, 5).
Pharmacodynamic interactions
In contrast to pharmacokinetics, there is a paucity of
data concerning pharmacodynamic interactions. These
involve changes in the response of the patient to a drug-
nutrient combination, without modification in pharma-
cokinetics of the drug or bioavailability of the nutrient.
Table 3 shows the two underlying mechanisms: antag-
onism and altered cellular transport systems (1).
The best known example of antagonism is Warfarin;
its anticoagulant effect is annulled or substantially
decreased by vitamin K. The vitamin K content of a
diet formula will directly and inversely influence the
degree of Warfarin anticoagulation (1, 8, 9). When a
patient is receiving oral anticoagulant therapy it is best
to avoid formulae containing more than 75 to 80 mg of
vitamin K/1000 Kcal (9). Another pharmacodynamic
interaction results from the interaction of the composi-
tion of an enteral formula to the absorption of
levodopa. Because levodopa shares the same carrier
across the blood–brain barrier, any dietary manipula-
tion affecting circulating neutral amino acids (valine,
leucine, isoleucine, tyrosine, and tryptophan), may
modulate the biologic and clinical effects of levodopa
(1, 11).
Recommendations of administering medication during
tube-feeding
. The pharmacist has valuable expertise in optimising
prescriptions.
192 ENTERAL FEEDING: DRUG/NUTRIENT INTERACTION
. Never add medications directly to the enteral
formula.
. Do not administer medications through the same
port of an enteral feeding tube as the feeding
solution.
. Minimise the likelihood of an interaction.
Procedures:
a) interrupt the tube feeding 2 h before and 2 h after
administering the drug and re-adjust the tube-feeding
schedule to accommodate the total 24 h requirements.
b) monitor blood levels more frequently if the prescribed
drug has a narrow therapeutic index.
c) observe the patient for unexpected changes in clinical
response (12–15).
. Factors that influence drug delivery include the
dosage form as well as the type and placement of
the distal tip of the tube (9, 15).
. Whenever possible use the liquid form of a drug
because it bypasses the dissolution process-a rate-
limiting step to absorption (12, 29). However, many
liquid medications are formulated for paediatric use;
thus, in order to meet the required dose for adults,
large volumes of the medication must be dispensed.
This often results in undesirable effects, such as
diarrhoea due to the excipient sorbitol.
. Check whether the drug formulation requires any
dilution prior to administration. Hypertonic,
irritating or viscous medications should be diluted
in at least 30 ml of water immediately before infusion
to avoid gastric irritation and diarrhoea. However, a
liquid formulation is not always available and
alternative methods of administration should be
considered in consultation with pharmacist (12).
. If a tablet is the only preparation available
consultation with the pharmacist is mandatory. The
tablet can be crushed into a fine powder and mixed
with water before delivery into the tube (12, 32),
however certain formulations cannot be crushed
(12, 32).
. Drugs in gelatinous capsules must never be forced
into a feeding tube; the capsule should be opened and
the content mixed with water before administration
(12). Omeprazole capsules can be opened but the
granules should never be crushed because they need
to reach the small intestine intact. One way to
proceed is to open the capsules, mix the granules
with 20 ml of an acidic fruit juice and then administer
by the feeding tube, though not through the feeding
port because most feeds are milk-based and their
mixing would cause tube clogging (12).
. Other forms not suitable for manipulation include
enteric coated drugs, sustained release tablets or
capsules, sublingual or buccal medications, and
effervescent tablets (1, 8, 9, 20, 32).
. Tubes must always be flushed with a minimum of
30 ml of room temperature boiled and cooled water
before and after administration of each medication
(8, 9, 12, 15, 16).
. To avoid drug–drug interaction, drugs must not be
mixed together, and at least 10 ml of water should
be used to flush the tube between each administration
(9, 10, 12, 32).
. Cytotoxic drugs should be handled with special care
(20, 32).
Conclusion
DNI, especially with enteral feeding, can affect quality
and cost/effectiveness in healthcare. The pharmacist on
the multiprofessional nutrition support team is best
suited to understand the pharmacology of a nutrient or
drug, the mechanism by which they may interact and
can assist in predicting or allowing early recognition of
an interaction. The team provides complementary
expertise thereby reducing the risk of avoidable compli-
cations, morbidity and mortality. However, our knowl-
edge about DNI still has many limitations.
There are so many ways for diet to influence the
outcome of disease or therapy that it must always be
considered as part of a therapeutic regimen. Reconsider
diet when drugs are not performing as expected (29).
Acknowledgements
The author wishes to thank ME Camilo, MD PhD and Mrs Pat
Howard, Dietician for their valuable insights and input.
References
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