Drug-Nutrient Interactions

Question 1

What are the factors related to nutrition support that may influence drug-nutrient interactions?

Answer 1

The type and site of access
Method of administration
Content of the PN or EN formulation

Question 2

How is a drug-nutrient interaction defined?

Answer 2

An event that occurs when a 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 3

What are the types of physical drug-nutrient interactions?

Answer 3

Precipitation in PN or EN formulations
Disruption of emulsion for ILEs or EN formulation
Altered viscosity, change in consistency, clumping, or curdling of EN formulation

Question 4

What are the variables to consider when assessing the risk of a physical drug-nutrient interaction?

Answer 4

The pH at which the drug and PN/EN formulation is most stable
Presence of cations and anions known to react chemically
Concentration and chemical complexity of nutrients
Time, temperature, and duration of exposure to one another

Question 5

What is a frequent outcome of physical drug-nutrient interactions?

Answer 5

Occlusion of the feeding access device

Question 6

What are visually evident physical changes in PN formulations that indicate incompatibility?

Answer 6

Turbidity
Haziness
Cloudiness
Color changes
Precipitate formation
Emulsion disruption in lipid-containing PN

Question 7

List some drug-nutrient physical interactions that result in a loss of drug or nutrient activity that requires chemical or molecular analysis for detection in which no visible changes occur in the product

Answer 7

Admixture of octreotide acetate to PN creates incompatibility due to development of a glycosyl octreotide conjugate and loss of drug activity.
Injectable multivitamins are compatible with PN formulation, but some vitamins (thiamin) have limited stability and begin to very quickly lose their activity once added to the PN formulation because of hydrolysis, photodegradation, or other forms of chemical degradation

Question 8

What factor(s) is most likely to result in occlusion of the vascular access device when a patient is receiving several drugs and PN through the VAD?
Scenario: Patient s/p hematopoietic cell transplant receiving PN with separate ILE and patient-controlled analgesia with morphine sulfate through his tunneled VAD. Ceftazidime, Fluconazole, and Foscarnet are administered through the VAD. Pt with increased calcium demand so calcium chloride 1gm q 8 hrs is ordered for adding to PN (due to shortage of calcium gluconate and bc patient requires high phosphate content in PN which would limit addition of calcium gluconate). Meds ordered for “minimum fluid”. VAD is double lumen, one lumen is occluded. Morphine is continued through the line; Foscarnet, Ceftazidime, Fluconazole, and PN are on hold until access can be obtained.

Patient was receiving a blood transfusion when the calcium dose was due, and was to receive platelets once the red cell transfusion was complete. Pt’s nurse co-infused calcium chloride with the PN, which contained above-standard amounts of potassium phosphate due to effects of Foscarnet. A 0.22-micron filter was on the PN lumen of a bifurcation device connected to the catheter lumen; however, there was no filter after the calcium mixed with the PN solution

Answer 8

Review administration regimen for physical interactions that occlude the VAD
Composition of PN and co-infused drug should be reviewed

Antibiotic Ceftazidine and Fluconazole are compatible for co-infusion with PN. Foscarnet can be incompatible with calcium-containing solutions and may cause problems if co-infused with PN containing calcium. High likelihood of calcium precipitating with phosphate when calcium chloride is co-infused with PN.

Altering the pH for this occlusion within the VAD to make the drug more soluble will likely clear the occlusion. Consider risk vs benefit of line salvage first. Confirm compatibility between catheter materials and recommended clearance solution.

With calcium-phosphate precipitate, decreasing the pH by instilling 0.1-N hydrochloric acid will increase calcium phosphate solubility and may be effective in clearing the occlusion.

Question 9

The presence of what specific nutrient component in EN formula seems to be a critical property for determining risk of developing a physical interaction?

Answer 9

Complex protein (intact or whole protein) (caseinates, soy, whey)

Question 10

Why is EN formula dilution not recommended?

Answer 10

Increases the risk of microbial contamination

Question 11

What two factors are of particular importance with drugs in liquid form in regard to their potential to cause drug-nutrient interaction?

Answer 11

Acidic pH and base components, especially sugar-water syrups, alcohol-containing elixirs, or oil-based products

Question 12

Why is the risk of undesirable interactions between drugs and EN formulations containing soluble fibers greater than with soy polysaccharide?

Answer 12

Soluble fibers have a propensity to form gels.

Question 13

How are physical drug-nutrient interactions best avoided?

Answer 13

By not allowing drugs to mix with either EN or PN formulations. Ideally drugs would be administered via a route other than the feeding administration device (VAD or feeding tube)

Question 14

What are the other available routes for medication administration other than the VAD or feeding tube?

Answer 14

Oral, rectal, transdermal, sublingual, intramuscular, subcutaneous

Question 15

What is the most effective method for preventing feeding tube occlusion related to medication administration in a patient receiving jejunal feedings to supplement inadequate oral intake associated with gastroparesis?
Scenario: patient w/ gastroparesis 2/2 T2DM. Thin liquids empty from the stomach with only slight delay; progression of thick liquids and solids into the duodenum is severely delayed. GJ tube is placed and patient is started on TF + thin liquid diet.

Answer 15

If patient is able to eat by mouth, medications should be given via the oral route as these do not cause tube occlusion. Medications taken with water should have minimal effect on gastric emptying compared with water alone, and thin liquids empty with only slight delay per the GI evaluation

Question 16

What is the usual fluid of choice for flushing VADs?

Answer 16

Sodium chloride 0.9%, but sometimes 5% dextrose is required

Question 17

What is the fluid of choice for flushing enteral feeding tubes?

Answer 17

Water

Question 18

What is the minimum recommended volume used to flush enteral feeding tubes in adults?

Answer 18

15 ml

Question 19

What should be done if a drug must be administered through the same device as the PN or EN formulation?

Answer 19

Feeding should be stopped, and the access device should be flushed before and after drug administration and between drugs if multiple drugs are administered

Question 20

What are other potential methods of preventing physical interactions with PN and EN formulations?

Answer 20

Altering the infusion time (cyclic regimen), altering the nutrition formulation (changing to hydrolyzed or free amino acid EN formula), or altering the drug

Question 21

Interactions that occur because a drug dosage form is altered are more likely to occur with EN or PN therapy?

Answer 21

EN therapy

Question 22

What are some alternate dosage forms that drugs are available in?

Answer 22

Enteric coated (to protect the drug from gastric acid, or to protect the stomach from an irritating drug)
Long acting (to reduce the number of daily doses)
Sublingual or rectal (to bypass first-pass metabolism in the liver)

Question 23

What can happen if you alter certain drug dosage forms?

Answer 23

Can dramatically increase or decrease drug bioavailability and trigger adverse effects or, conversely, destroy the active ingredient

Question 24

What is the most common method of altering a dosage form?

Answer 24

Crushing or dissolving solid dosage forms to create a liquid for administration via the feeding tube

Question 25

How should solid dosage forms that are appropriate to crush/alter be prepared for administration in the feeding tube?

Answer 25

Prepared as a very fine powder and mixed with warm water before administration. Many capsules may be opened and the contents administered after forming a slurry with water from the powder or finely crushed solids

Question 26

Why should special dosage forms such as long-acting, sustained-release, slow-release, or delayed-release not be crushed or dissolved?

Answer 26

They contain several doses in 1 tablet and are designed to slowly release in the GI tract, often over 12-24 hours. Crushing may cause immediate release of the total drug dose, increasing the risk of toxicity and reducing efficacy

Question 27

Abbreviations to be aware of in a drug that indicates they need to be taken intact and should not be crushed or dissolved for administration:

Answer 27

CD, CR, ER, LA, SA, SR, TR, XL, XR

Question 28

Why should enteric coated (denoted as EC after the drug name) drugs generally not be altered for administration

Answer 28

The coating is intended to protect a drug from destruction by gastric acid or to protect the stomach from irritation caused by the drug.

Question 29

What should be done for administration of enteric coated drugs into the jejunum?

Answer 29

Administration into the jejunum negates the need for an enteric coating since the jejunum is where the coating is designed to dissolve. Can dissolve the coating in bicarbonate solution, then crush the tablet. Can be a slow process (30-45 minutes) and caution is still required to avoid tube occlusion

Question 30

What are film coatings on medications?

Answer 30

Used to make tablets easier to swallow or to mask unpleasant taste, but they do not impart special characteristics such as those associated with enteric coating. Often remain as undissolved pieces in water and can occlude the feeding tube

Question 31

Which of the available dosage forms of Lansoprazole should be ordered, and how should it be administered through a nasal-jejunal feeding tube?
Scenario: Pt receiving Lansoprazole (Prevacid) d/t GI bleed. Being fed via small-bore nasal-jejunal tube d/t poor nutrition status, inability to take oral diet, and aspiration risk while on mechanical ventilation. Extubated and IV lansoprazole stopped

Answer 31

Discuss options for acid suppression and address whether acid suppression needs to be continued once off mechanical ventilation and out of ICU. If acid suppression is to continue, the histamine-2 receptor antagonist on the hospital’s formulary may be adequate. Lansoprazole is problematic for administration through small-bore feeding tube. Either an extemporaneously prepared oral suspension or therapeutic alternative should be considered to avoid occlusion of the feeding tube.

Question 32

Why is Lansoprazole problematic for administration through small-bore feeding tube using commercially available dosage forms?

Answer 32

Available as a delated-release capsule and as a delayed-release ODT. These dosage forms should not be crushed because of the delayed release characteristic. Capsule can be opened and intact granules administered with apple juice (40ml) via feeding tube, however the small-bore tube is not of adequate size.

Question 33

What is the adequate feeding tube size for administration of intact granules from the capsule form of a medication?

Answer 33

16 Fr

Question 34

Why should IV dosage forms not be administered via GI tract?

Answer 34

They are poorly suited to withstand gastric acidity and enzyme activity within the GI tract. Substantial drug loss can occur. IV electrolyte preparations are an exception.

Question 35

What is a potential side effect of using oral liquid dosage forms of certain medications?

Answer 35

Can have high osmolality and result in diarrhea or cramping. Osmolality of oral liquids and IV drugs often exceeds 1000 mOsm/kg.

Question 36

What can help reduce the risk of GI intolerance with hyperosmolar products?

Answer 36

Diluting with water before administration reduces the osmolality

Question 37

What sweetening agents often used in oral liquid dosage forms contribute to increased osmolality?

Answer 37

Mannitol, sucrose, and sorbitol

Question 38

Why is sorbitol a particularly troublesome sweetening agent when added to oral liquid dosage forms?

Answer 38

The cumulative daily dose of sorbitol from oral liquid drugs can reach 20-50 gm, which is an amount commonly used as an osmotic laxative. Sorbitol doses of only 5-10 mg daily cause a considerable portion of people to experience bloating and flatulence

Question 39

Why do pharmacokinetic drug-nutrient interactions occur?

Answer 39

Can occur as the result of multiple factors: administration of EN or PN, the drug, the PN or EN formulation, the disease process (especially if it affects protein status, organ perfusion, and GI motility)

Question 40

What is bioavailability?

Answer 40

The amount of drug that reaches systemic circulation after administration

Question 41

What factors can cause product loss that decrease bioavailability?

Answer 41

Drug or nutrient loss during administration, adverse pH effects, complex formation between nutrients and drug, presystemic metabolism in the gut mucosa, and hepatic first pass metabolism

Question 42

What are 2 examples of drugs with a “local” effect?

Answer 42

Antacids and sucralfate. They have no therapeutic effect with postpyloric delivery because they act locally in the stomach

Question 43

Slow gastric emptying increases the extent of absorption for which nutrients?

Answer 43

Those that benefit from acid exposure (iron, calcium, magnesium) and those that undergo active absorption by a saturable mechanism in the upper small bowel (riboflavin)

Question 44

The effect of delivery into the small bowel on drugs largely depends on what?

Answer 44

The drugs’ solubility and need for acid exposure for absorption

Question 45

Clinical experience suggests that holding EN administration how frequently for drug administration is likely to result in inadequate nutrition support and deterioration of nutrition status unless a volume-based feeding protocol is used?

Answer 45

Holding EN administration for approximately 1-2 hours every 6-8 hours

Question 46

For PN formulations, what are drug-related pharmacokinetic DNI factors largely associated with?

Answer 46

Stability of the IV dosage form and the potential for loss of drug activity due to chemical reactions (photodegradation, oxidation, hydrolysis)

Question 47

What is presystemic metabolism?

Answer 47

Metabolism that occurs before reaching systemic circulation, occurs in both the gut mucosa and liver

Question 48

Estimated that what % of drugs currently available are metabolized by CP450 isoenzymes and which interaction is a classic example of this?

Answer 48

60% of drugs. Grapefruit juice inhibits the isoenzyme CYP3A4, thereby increasing serum levels of drugs normally metabolized by this isoenzyme

Question 49

Consistent intake of an EN formulation containing __ mcg of vitamin K per 1000 kcal is not expected to cause warfarin resistance

Answer 49

<100 mcg of vitamin K per 1000 kcal

Question 50

What administration regimen of Phenytoin with EN produces the most consistent results?

Answer 50

Holding EN for at least 1 hour and possibly 2 hours before and after phenytoin administration