Chapter 18: Drug-Nutrient Interactions

Question 1

Define DNI.

Answer 1

Drug Nutrient Interaction ASPEN defines DNI as “an event that occurs when nutrient availability is altered by a medication, or when a drug effect is altered or an adverse reaction is caused by the intake of nutrients.’

Question 2

The presence of XXXX seems to be a critical property for determining risk of developing a physical interaction.

Answer 2

Complex protein (ie: intact or whole protein)

Question 3

XXXX, XXXX, and XXXX of the EN formulation have not been shown to affect the risk of physical interactions with drugs in studies reported in the literature.

Answer 3

Fiber content N content Dilution of the EN formulation

Question 4

What two factors are of particular importance with drugs in liquid form?

Answer 4

1. Acidic pH 2. Base components, especially sugar-water syrups, alcohol-containing elixirs, or oil-based products.

Question 5

(TRUE/FALSE) 1/3 of drugs in liquid dosage have demonstrated undesirable effects with at least 1 EN formulation.

Answer 5

TRUE.

Question 6

(TRUE/FALSE) Physical interactions are best avoided by not allowing drugs to mix with either PN or EN formulations. Ideally, drugs should be administered via a route other than the feeding administration device.

Answer 6

TRUE.

Question 7

When a drug must be administered through the same device as the PN or EN formulation, what is the procedure?

Answer 7

The feeding should be stopped, and the access device should be flushed with fluid that is compatible with the PN or EN formulation as well as the drug. The access device should be flushed before and after drug administration and between drugs if multiple drugs are administered.

Question 8

What is the ideal fluid of choice for flushing VADs?

Answer 8

0.9% sodium chloride, or sometimes 5% dextrose solution is required

Question 9

What is the ideal fluid of choice for flushing EN tubes?

Answer 9

Water

Question 10

(TRUE/FALSE) Acidic products, such as carbonated beverages and cranberry juice may be used for flushing.

Answer 10

FALSE. They can be particularly problematic.

Question 11

(TRUE/FALSE) The minimum recommended volume used to flush enteral feeding tubes in adults is 30 mL.

Answer 11

FALSE. 15 mL; although usually larger volumes are often used.

Question 12

What type of medications (as a general rule), should not be crushed or dissolved?

Answer 12

Special dosage forms such as long-acting, sustained-release, slow-release, or delayed-release containing several doses in 1 tablet/capsule Watch for: CD, CR, ER, LA, SA, SR, TR, XL, or XR (generally these need to be taken intact)

Question 13

(TRUE/FALSE) Administration into the jejunum negates the need for an enteric coating since the jejunum is where the coating is designed to dissolve.

Answer 13

TRUE. Dissolving the coating in bicarbonate solution, then crushing the table is acceptable for jejunal administration, although the process can be slow (30 to 45 minutes) and caution is still required to avoid tube occlusion.

Question 14

(TRUE/FALSE) Film coatings are used to make tablets easier to swallow or to mask unpleasant taste. They also impart special characteristics such as those associated with enteric coatings.

Answer 14

FALSE They DO NOT impact special characteristics. Crushed film-coated tables should not result in altered drug activity or increased risk of adverse effects. They can be problematic because they often remain as undissolved pieces that become sticky in water and can occlude the feeding tube.

Question 15

(TRUE/FALSE) Intact pellets may be administered through the feeding tube, provided the pellets are small enough to completely pass through the tube.

Answer 15

TRUE. Usually a larger tube (min. 16-Fr) is necessary for successful administration of these dosage forms.

Question 16

What liquid would you use to administer a drug with intact pellets?

Answer 16

Acidic juice as the vehicle for microencapsulated pieces as it should reduce the risk of the beads or pellets sticking to the tube. NOTE: Water should be used to clear the tube of the EN formulation before and after administration of the acidic-juice mixture to avoid physical DNIs between the EN formulation and an acidic product.

Question 17

What is the recommendation administration for pancreatic enzmyes?

Answer 17

With no viable options, it may be necessary to dissolve an enteric coating on the beads or pellets in a sodium bicarb. solution, then crush and administer the drug with a small volume of sodium bicarbonate solution.

Question 18

(TRUE/FALSE) Diluting hyperosmolar products with water before administration reduces the osmolality and may reduce the risk of GI intolerance.

Answer 18

TRUE.

Question 19

(TRUE/FALSE) Proper tube flushing cannot prevent pharmaceutical interactions. However, flushing with adequate quantities of water remains an important technique to prevent concomitant physical interactions

Answer 19

TRUE. Pharmaceutical interactions may also be minimized by using alternate routes of administration or by using a therapeutic alternative that is available in a form conductive to administration via the feeding tube.

Question 20

Define pharmacokinetics.

Answer 20

Refers to studies of the time course for drug absorption, distribution, metabolism, and excretion. The term can also be applied to nutrients because the same processes occur with nutrients.

Question 21

Define bioavailability.

Answer 21

Describes the amount of drug that reaches systemic circulation after administration.

Question 22

List some examples of what can decrease bioavailability.

Answer 22

• Drug or nutrient loss during administration
• Adverse pH effects
• Complex formation between nutrient(s) and drug
• Presystemic metabolism in the gut mucosa (CYP450)
• Hepatic first-pass metabolism

Question 23

(TRUE/FALSE)

The potential for chemical reactions and stability issues exists whenever a solid dosage form of drug is made into a liquid form.

Answer 23

TRUE.

Water tends to accelerate chemical reactions that result in loss of drug activity.

Question 24

Rapid gastric emptying accompanied by rapid GI transit can result in XXX absorption because…..

Answer 24

Poor absorption because there is insufficient contact time between the drug/nutrient and the absorptive surface of the small bowel.

Question 25

(TRUE/FALSE)

Delivery of the EN formulation and drugs into the small bowel bypasses problems with gastric emptying.

Answer 25

TRUE.

Question 26

Where does presystemic metabolism occur?

Answer 26

Gut mucosa and liver

Question 27

Define CYP450 enzyme system.

Answer 27

• Includes many isoenzymes involved in drug metabolism and is a major component of presystemic metabolism.
• ~60% of drugs currently available are metabolized by these isoenzymes, specifically CYP3A4

Question 28

What is a classic example of CYP450-mediated DNI?

Answer 28

Drug interactions with grapefruit juice

Grapefruit juice inhibits the isoenzyme CYP34A, thereby increasing serum levels of drugs normally metabolized by this isoenzyme.

Question 29

What is P-glycoprotein?

Answer 29

• The best-known transporter
• Serves as an efflux mechanism to pump xenobiotics (drugs and other chemicals/substances not normally present in the body), out of the cells and prevent entry to the compartment that the cells protect.
• Located on the luminal surface of cells lining the small bowel and prevents systemic absorption of certain drugs.

Question 30

(TRUE/FALSE)

The alterations in body composition associated with malnutrition, edema, increased body water and decreased lean muscle may affect pharmacokinetics parameters.

Answer 30

TRUE.

Question 31

What is phenytoin prescribed for?

What methods are used to manage DNIs with EN and this medication?

Answer 31

Anti-epileptic drug, also used as an anticonvulsant

None of the methods used are completely reliable, and monitoring of serum phenytoin concentrations is highly recommended and consistency of administeration is important

• Holding administration of the EN for at least 1 hour, and possibly 2 hours, before and after phenytoin administration, seems to produce the most consistent results
• Dilution of phenytoin suspension is also recommended when the suspension is administered through a feeding tube

Question 32

What is carbamazepine used for?

What are the methods used for controlling DNIs with EN and this drug?

Answer 32

Anticonvulsant

The first choice of methods is:

• Adequate dilution of the suspension (or slurry from a crushed tablet) prior to administration and adequate flusing after the dose
• Dilution should be at least 1:1, preferably 3:1, with water if administered via a feeding tube because drug loss in the feeding tube seems to be reduced with dilution.

When that fails (in postpyloric administration):

• It would be reasonable to hold feedings before and after drug administration in this population.

Question 33

What method is recommended for preventing DNIs with fluoroquinolone antibiotics?

Answer 33

Holding feedings remains a potential method for mitigating EN interactions with ciprofloxacin or nofloxacin; however, holding feedings with other fluoroquinolones should not be done routinely.

NOTE: Many facilities follow a policy of holding EN for at least 1 hour before a fluoroquinolone dose and 2 hours after each dose, as recommended previously. This approach does seem to minimize the effects; however the data is very limited especially in TF patients.

Question 34

What methods are used for mitigating DNIs with warfarin with low vitamin K intake?

Answer 34

• No definitive recommendations can be provided associated with relatively low vitamin K intake.
• Response to warfarin therapy must be closely monitored with EN therapy is started, stopped, or altered
• Holding EN around administration of warfarin through a feeding tube should NOT effect bioavailability, and they did NOT recommend holding feedings to mitigate warfarin-EN interactions

Question 35

(TRUE/FALSE)

One proprosed mechanism for warfarin resistance with low vitamin K intake is binding of warfarin to a component of the EN formulation, most likely protein.

Answer 35

TRUE.

Use of a free AA (elemental) TF is expected to prevent this interaction; however, that is not recommended.

Practitioners may elect to manage the interaction by other methods (increase dose or use another therapy)

Question 36

What are potential methods of mitigating the warfarin-EN interaction?

Answer 36

• Rapidly administering a concentrated form of the drug to minimize contact with the feeding tube
• Separating warfarin administration from EN admin (holding EN for at least 1 hour before and after, is second approach)
• Increasing the warfarin dose until a therapeutic PT/INR is achieved, OR
• Changing to an alternative anticoagulation therapy that does not interact with EN therapy.

*Minimizeing contact with the feeding tube has a low potential to cause unintended consequences and is a reasonable first approach.