Download Phenytoin

Effect of
nutrient-devices
on drugs
Skouroliakou M.
Effect of nutrient-devices
on drugs
• One of the most frequent drug-related
problems in patients receiving clinical
nutrition is drug interactions with enteral or
parenteral nutrition, and inappropriate drug
administration techniques
Effect of nutrient-devices
on drugs
The problem (1)
• Not much is known about drug and enteral or
parenteral feed incompatibilities. This is due
partly to the huge variability in composition of EN
and, especially, TPN solutions, and the range and
concentration of drugs which may be administered
simultaneously
Effect of nutrient-devices
on drugs
The problem (2)
• One can find few things in current literature or in
the manufacturer’s product summary, therefore
most recommendations are theoretical
• Usually, drugs are not licensed for administration
in EN or PN, so pharmacists need to combine
theory with empiricism, knowing that in most
cases they cannot rely on published data to
confirm the safety of their actions.
Effect of nutrient-devices
on drugs
European Association of
Hospital Pharmacists
Amsterdam 2001
General mechanisms of interactions
between nutrients and drugs (1)
• stimulation of splachnic capillary blood flow
(increase in first-pass effect)
• chelation of drug molecules by minerals such as
calcium and iron (eg. quinolones)
• competing with the action of the drug
(eg. warfarin-vita K)
Effect of nutrient-devices
on drugs
General mechanisms of interactions
between nutrients and drugs (2)
• changing the pH of the GI tract to increase or
decrease absorption
• inhibiting or enhancing drug metabolism
• changing GI motility to increase or decrease
absorption
• enhancing drug solubility
Effect of nutrient-devices
on drugs
Role of therapeutic drug monitoring
• Appropriate monitoring for altered response or
altered plasma levels of drugs (especially those
with a narrow TI) is of vital importance. If drug
interactions are not identified but doses are
adjusted due to lack of therapeutic response,
toxicity may ensue when feeds are discontinued.
Effect of nutrient-devices
on drugs
Drug administration in enteral nutrition
General considerations:
• Formulation to be used
• Interaction with the feed or other drugs
• Timing of drug administration
• Moreover, type of tube, placement site, and the
site of drug absorption
Effect of nutrient-devices
on drugs
Formulations commonly used in EN
• Liquid preparations are easy to administer through
a tube and are usually preferred to other forms.
• soluble tablets
• dispersible tablets
• capsule contents
• When changing formulations, drugs may require
dosage or frequency adjustments
Effect of nutrient-devices
on drugs
Interactions in enteral nutrition
• Interactions most usually encountered are related
to drug precipitation, and chelation with mineral
cations, which may result in inadequate absorption
of the drug and impaired therapeutic effect
• Furthermore, these may lead to tube blockage
(~15 % of patients) which occupies nursing time,
limits feed and drug intake, and increases trauma
to the patient
Effect of nutrient-devices
on drugs
Increased probability of clinically
significant interactions with:
• Drugs interacting with food, vitamins or
electrolytes
• Drugs that need to be given on an empty stomach
• Drugs which are given in liquid form particularly
when multiple drugs or high volumes are given
this way
• Drugs with a narrow therapeutic index
Effect of nutrient-devices
on drugs
Examples of interactions (1):
Theophylline
• The bioavailability of theophylline may be altered
by food. The mechanism may be related to
changes in metabolism as a result of nutrient
effects on stimulating and inhibiting cytochrome
P450. Varying effects have been reported in
patients on enteral feeds
• Feeding should be stopped for one hour before and
two hours after dose and drug levels should be
monitored
Effect of nutrient-devices
on drugs
Examples of interactions (2):
Aluminium-containing antacids
• While receiving high protein enteral feeds an
obstructing protein-aluminium complex
oesophageal plug in patients may be formed
• Antacids should not be given to patients receiving
high molecular weight protein feeds or, if
necessary, the feed should be stopped and the tube
thoroughly flushed.
• Antacids may also bind phosphate from enteral
feeds, thereby causing hypophosphataemia
Effect of nutrient-devices
on drugs
Examples of interactions (3):
Quinolone antibiotics
• Ciprofloxacin and ofloxacin possess good
absorption characteristics, so they are usually
given enterally rather than intravenously.
However, in patients receiving enteral feeding,
studies suggest that significantly lower plasma
concentrations than expected are attained. This is
due to the formation of insoluble chelates with
divalent ions (calcium, magnesium, etc) in the
feeds, thus reducing absorption from the GI tract
Effect of nutrient-devices
on drugs
Examples of interactions (4):
Quinolone antibiotics
• When a severe infection is being treated it has
been suggested that NG tube administration to
these patients should not be used unless facilities
for plasma concentration monitoring are available.
In other patients, consideration may be given to
prescribing larger doses to be given through the
enteral feeding tube.
Effect of nutrient-devices
on drugs
Examples of interactions (5):
Quinolone antibiotics
• Although ofloxacin is considered to exhibit this
phenomenon to a lesser extent, the interaction is
thought to be a class effect and should be managed
accordingly
Effect of nutrient-devices
on drugs
Examples of interactions (6):
Phenytoin
• Phenytoin may perhaps be the most researched
drug in respect of its interactions with enteral
feeding. Significant problems in attaining and
maintaining therapeutic levels of phenytoin may
arise in clinical practice, and various courses of
action have been suggested in order to minimize
this effect
Effect of nutrient-devices
on drugs
Examples of interactions (7):
Phenytoin
• Administration of the undiluted suspension
without flushing the tube first, may result in a 75%
loss of the initial dose
• Administration of the liquid without shaking it
first, may result in variable absorption due to its
viscosity
Effect of nutrient-devices
on drugs
Examples of interactions (8):
Phenytoin
• Factors that may inhibit proper absorption of the
drug include:
• binding to the feeding tube
• binding to proteins or electrolytes in the formula
• inadequate dissolution
• decreased transit time
Effect of nutrient-devices
on drugs
Examples of interactions (9):
Phenytoin
• Further problems occur when the patient also
receives other drugs which interact with
phenytoin, or when he/she is hypoalbuminaemic.
The result of such multiple interactions may
sometimes be unpredictable
Effect of nutrient-devices
on drugs
Examples of interactions (10):
Phenytoin
Recommendations include (A):
• Phenytoin to be administered as a single daily
dose
• Enteral feeding to be stopped two hours before
administration of the drug and continue two hours
after
• Tube to be flushed with adequate amounts of
water before and after administration
Effect of nutrient-devices
on drugs
Examples of interactions (11):
Phenytoin
Recommendations include (B):
• The liquid should be shaken before use
• Dilution of the suspension with at least equal parts
or 20ml of water
• Serum level concentrations should be closely
monitored especially when changing from one
dosage form to another
Effect of nutrient-devices
on drugs
Drug administration in TPN
• When possible, drugs should not be given
simultaneously with the TPN solution
• Y-site connection should only become a necessity
when there is no other route or parenteral access
available and when a multi-lumen catheter is being
used to full capacity
Effect of nutrient-devices
on drugs
Interactions in total parenteral nutrition
The most frequently encountered drug-TPN solution
interactions result in:
•loss of stability
•precipitation of the admixture
which may minimize absorption of the drug by the
patient
Effect of nutrient-devices
on drugs
Factors which may largely affect
interactions between drug-TPN solution
(1)
•
•
•
•
composition of TPN regimen
contact time between drug and TPN solution:
brand and concentration of drug added
exposure of admixture to light and temperature
Effect of nutrient-devices
on drugs
Factors which may largely affect
interactions between drug-TPN solution
(2)
For 3-in-1 TPN admixtures containing fat emulsion:
• stability of the emulsion
• bioavailability of drug from emulsion
• formation of precipitates
Effect of nutrient-devices
on drugs
Mixing drugs with TPN solutions (1)
• A large number of the various substances found in
a TPN solution may interact with drug additives.
In the case of 3-in-1 admixtures, the potential risk
of incompatibility and stability problems is even
greater due to the addition of a fat emulsion. It has
been recommended that no other drugs or
solutions should be added to fat solutions due to
the risk of disturbing the stability of the emulsion
or affecting the bioavailability of the drug
Effect of nutrient-devices
on drugs
Mixing drugs with TPN solutions (2)
• Mixing drugs with TPN solutions cannot be
recommended without stability or compatibility
data on specific TPN regimens and drug
concentrations
• Exposure to temperature and light, as well as
prolonged contact time of a drug-TPN admixture
may increase the risk of stability and compatibility
problems
Effect of nutrient-devices
on drugs
Poor education
• Nursing staff who routinely administer drugs via
feeding tubes usually possess inadequate level of
knowledge
• Clinical practice is based on "trial and error“, little
use or development of guidelines
Effect of nutrient-devices
on drugs
Educational role of pharmacists (A)
• Those who consult pharmacy staff were found
more likely to use appropriate formulations and
reported less obstructions of feeding tubes
• Practice could be improved by active involvement
of pharmacists in establishing guidelines and
training nurses
Effect of nutrient-devices
on drugs
Educational role of pharmacists (B)
• Advising on suitable routes of drug
administration, formulation or alternative
preparations
• Advising on drug administration timing
• Educating nursing staff about administration
techniques
• Assisting to the development of local guidelines
• Providing other useful information
Effect of nutrient-devices
on drugs
u
Sources of info
• Ask the manufacturer!
• ESPEN, ASPEN, or other local
organizations’ publications
• Drug databases over the internet or in CDROMs