The Dosing of Medications in Patients Receiving … Enteral Nutrition Support Handbook Patient Resources 1. Health Facts for You: Enteral Feeding: Gastrostomy Tube Feeding #295 2

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Dosing of Medications in Patients Receiving Continuous Enteral Feedings – Adult –

Inpatient Clinical Practice Guideline

Table of Contents

EXECUTIVE SUMMARY ................................................................................................................................... 2

SCOPE .............................................................................................................................................................. 3

METHODOLOGY .............................................................................................................................................. 3

DEFINITIONS .................................................................................................................................................... 3

INTRODUCTION ............................................................................................................................................... 3

RECOMMENDATIONS ..................................................................................................................................... 4

Table 1: Medications Interacting with Continuous Enteral FeedingsMedication ......................................... 5

UW HEALTH IMPLEMENTATION .................................................................................................................. 24

APPENDIX A. EVIDENCE GRADING SCHEMES .......................................................................................... 25

REFERENCES ................................................................................................................................................ 26

CPG Contact for Changes: CPG Contact for Content: Name: Philip Trapskin, PharmD Name: Sara Shull, PharmD, MBA Phone Number: 263-1328 Phone Number: 262-1817 Email Address: [email protected] Email Address: [email protected]

Guideline Author(s): Coordinating Team Members: Jeff Fish, PharmD Sara Shull, PharmD, MBA, BCPS David Hager, PharmD, BCPS Melissa Heim, PharmD Suppachai Insuk, PharmD Sara Shull, PharmD, MBA, BCPS

Committee Approvals/Dates: Nutrition Support Committee: November 2014 Pharmacy and Therapeutics: January 2011, November 2014, September, 2015

Release Date: September 2015 Next Review Date: September 2018

Note: Active Table of Contents - Click to follow link

Copyright © 2015 University of Wisconsin Hospitals and Clinics AuthorityContact: Lee Vermeulen, [email protected] Last Revised: 09/[email protected]

mailto:[email protected]

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Executive Summary Guideline Overview: The purpose of this guideline is to provide recommendations for administering oral medications in a patient concurrently receiving enteral feedings. The goal of the guideline is to prevent or minimize interactions between medications and nutritional feeds in order to maximize absorption and clinical benefit of medications.

Key Practice Recommendations1-3 This clinical practice guideline is intended to establish a consistent, efficient, and safe standard for the administration of oral medications concurrently with enteral feedings to patients at UWHC. See Table 2 and Figure 1 for evidence classifications.

1. All patients receiving enteral feeds and medications should be assessed for potential interactionsand their severity. (Class B)

2. When possible, separate the administration of feeds and medications. (Class A)3. Use immediate release, non-enteric coated formulations when administering medications with

continuous enteral feeds (Class B)4. Enteral tubes should be flushed with water (at least 15 mLs) before and after medications

administration. (Class A)5. Patients should be monitored periodically for appropriate clinical response to medications (Class

B)

Summary of key recommendations for management of medications interacting with continuous enteral feedings2 (See Table 1 for complete recommendations)

1. Increase medication dose:1.1. ciprofloxacin (mild-to-moderate infections) (Class IIa Level of Evidence B)

2. Increase frequency of medication:2.1. If changing from extended release formulation:

2.1.1. carbamazepine and phenytoin (Class IIa, Level of evidence B) 2.1.2. diltiazem and divalproex/valproic acid (Class IIB, Level of Evidence C)

2.2. Phosphate binders: calcium acetate, lanthanum, sevelamer (all Class IIb, Level of Evidence C) 3. Hold tube feedings for a period both before and after medication administration:

3.1. penicillin V, phenytoin (one alternative) , theophylline (all Class IIa, Level of Evidence B)3.2. levothyroxine (if giving concomitantly for >7 days (Class IIa, Level of Evidence C)3.3. warfarin (one alternative)(Class IIb, Level of Evidence B)3.4. itraconazole, levofloxacin (mild-to-moderate infections), tamsulosin,, voriconazole (all Class IIb,

Level of Evidence C) 4. Administer medication with enteral feeding:

4.1. atovaquone (Class IIa,Level of Evidence B),4.2. posaconazole (or give with canola oil) (Class IIb,Level of Evidence B)

5. Do not give medication via enteral route / down enteral tube. Use an alternative agent:5.1. ciprofloxacin (severe infection give IV; do not give via tube ending in jejunum) (Class I, Level of

Evidence B) 5.2. phenytoin (one alternative is give fosphenytoin/phenytoin IV) (Class IIa, Level of Evidence B) 5.3. levofloxacin (severe infection give IV; do not give via tube ending in jejunum) (Class IIb, Level of

Evidence C) 5.4. dabigatran (do not open capsule) (Class III, Level of Evidence A) 5.5. rivaroxaban (use alternative anticoagulant if enteral tube ends distal to the stomach) (Class

III,Level of Evidence B) 5.6. sucralfate (give proton pump inhibitor or histamine-2 receptor antagonist) (Class III, Level of

Evidence C)


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Companion Documents 1. Table 1. Medications Interacting with Continuous Enteral Feeds2. Appendix A. Medication Administration via Enteral Tubes

Pertinent UW Health Policies & Procedures 1. Adult Enteral Nutrition Support Handbook

Patient Resources 1. Health Facts for You: Enteral Feeding: Gastrostomy Tube Feeding #2952. Health Facts for You: Enteral Feeding: Jejunostomy Tube Feeding #2963. Health Facts for You: Enteral Feeding: Dobhoff Tube Feeding #5969

Scope To establish recommended dosage adjustments for a pre-defined list of oral medications that may interact with enteral nutrition for adult patients only.

Methodology

A PubMed search of the English-language literature was performed to identify primary literature on enteral nutrition. Specific medications researched were cross referenced by using MeSH Database headings. Those medications having no primary or secondary published literature identifying the presence or absence of interactions with continuous enteral nutrition were identified. The manufacturers of these medications were then contacted. If no specific recommendations were made by the pharmaceutical manufacturer concerning administration of their product with continuous enteral nutrition, experts were asked to provide recommendations on administration of drug therapy and continuous enteral nutrition.

The strength of general practice recommendations is based on a modified version of the method used by the Agency for Healthcare Research and Quality (AHRQ), U.S. Department of Health and Human Services and adopted by the American Society for Parenteral and Enteral Nutrition (ASPEN) to classify evidence supporting recommendations in enteral nutrition practice recommendations published in 2009.

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A modified Grading of Recommendations Assessment, Development and Evaluation (GRADE) developed by the American Heart Association and American College of Cardiology (Appendix 1.) has been used to assess the Quality and Strength of the Evidence for specific medications in this clinical practice guideline (Figure 1).

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Definitions

Enteral Nutrition: Nutrition provided through the gastrointestinal tract via a tube, catheter, or stoma that delivers nutrients distal to the oral cavity.

Continuous Enteral Feedings: Mode of enteral feedings that provides the daily nutritional goal continuously over 24 hours.

Introduction Interactions between oral medications and enteral nutrition have been appreciated for many years, yet specific recommendations on how to administer these medications to patients is lacking in the literature. Ensuring that medications delivered to a patient will be adequately absorbed is often difficult. With the increased emphasis on changing medication from parenteral to oral dosage formulations to manage infection risk, afford patients greater mobility, and reduce cost, this is becoming more of a consideration.

2,5,6

Since enteral tubes are placed into different sites of the gastrointestinal tract (ie. stomach, duodenum, jejunum), drug absorption from different sites was included, if available. Evidence derived from patients who have received Roux-en-Y gastric bypasses was included to help determine absorption of medications from the jejunum.


https://uconnect.wisc.edu/clinical/references/clinical-nutrition-resources/nutrition-guidelines-and-enteral-formularies/resources/name-33912-en.file

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By recognizing the severity of potential drug-nutrient interactions, practitioners may prevent possible interactions and ultimately improve patient outcomes.

2 The following guidelines were generated to aid practitioners in their decision on

how to best administer medications to patients receiving continuous enteral nutrition. All included medications have been designated with one of the following recommendations: 1. adjust the dose of the oral medication; 2. no dose adjustment necessary; 3. hold enteral nutrition around the administration of the medication; or 4. hold the oral medication while the patient is on enteral nutrition or use an alternate administration route for the medication. Holding enteral nutrition was recommended conservatively, due to the risk of not meeting nutritional goals.

Recommendations1

1. Do not add medication directly to an enteral feeding formula. (Class B)2. Avoid mixing together medications intended for administration through an enteral feeding tube given the risks

for physical and chemical incompatibilities, tube obstruction, and altered therapeutic drug responses (ie, do notmix medications together, but do dilute them appropriately prior to administration). (Class B)

3. Each medication should be administered separately through an appropriate access. Liquid dosage formsshould be used when available and if appropriate. Only immediate-release solid dosage forms may besubstituted. Grind simple compressed tablets to a fine powder and mix with sterile water. Open hard gelatincapsules and mix powder with sterile water. (Class B)

4. Prior to administering medication, stop the feeding and flush the tube with at least 15 mL water. Dilute the solidor liquid medication as appropriate and administer using a clean oral syringe (≥ 30 mL in size). Flush the tubeagain with at least 15 mL water taking into account patient’s volume status. Repeat with the next medication (ifappropriate). Flush the tube one final time with at least 15 mL water. (Class A)

5. Restart the feeding in a timely manner to avoid compromising nutrition status. Only hold the feeding by 30minutes or more when separation is indicated to avoid altered drug bioavailability. (Class A)

6. Consult with a pharmacist for patients who receive medications co-administered with EN. (Class C)


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Table 1: Medications Interacting with Continuous Enteral FeedingsMedication

Documented interaction with continuous enteral feedings / site of enteral

access

Documented Food Interaction Recommendation:

Adjustments with regards to continuous enteral feedings

Reference

Acyclovir No data available. No interactions.

Suggest no dose adjustment required.

(Class IIb, Level of Evidence C)

7

Amantadine No data available No interaction with food. Solubility

increases with water.

Suggest no dose adjustment required


8

Amlodipine No data available No interactions with food



9

Amiodarone No data available.

Food may enhance rate and extent of absorption. After consuming a high-

fat meal, the AUC of amiodarone increased 2.3 times the fasting and

the Cmax increased 3.8 times the fasting value.


(Class IIb Level of Evidence C)

10

Amoxicillin/ Clavulanate

No data available.

Optimally administered at the start of a standardized meal. Absorption of

amoxicillin is decreased in the fasting state. High fat meals decrease the

absorption of the clavulanate component.



11

Apixaban No data available No interactions with food.



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Reference

Atovaquone

The mean AUC of atovaquone suspension in

serum after enteral administration with

concomitant Sustacal Plus enteral feeds was significantly greater when compared with

fasting.

Food significantly increases bioavailability. Therapeutic plasma

concentrations may not be achieved if administered during fasting.

Suggest no dose adjustment required, but it needs to be

administered with tube feedings for maximal absorption.

(Class IIa, Level of Evidence B)

13

Azithromycin No data available.

Food produces no clinically significant change in bioavailability.

Tablets: Food was shown to increase Cmax by 23% but had no effect on

AUC. Suspension: Food increased Cmax by

56% and AUC was unchanged.



14

Baclofen No data available No interactions



15

Calcium Acetate No data available. Therapeutic effect of drug requires

that it be taken with food.

Suggest scheduling 4-6 times per day for maximum effect. If a

combination of phosphate binders is needed, they should be

scheduled at different times


16


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Reference

Carbamazepine

Administration of the commercially available

suspension through the NGT results in drug adherence to the polyvinyl chloride walls of the feeding tubes resulting in

inadequate drug delivery. The bioavailability of

carbamazepine suspension with enteral feeding

administration was 90.1% of that during fasting. Although absorption of carbamazepine

suspension was generally slower and slightly diminished

during NGT feeding, this interaction may lessen unwanted side effects.

Carbamazepine should be given diluted to prevent the significant loss seen when

given undiluted.

Food decreases bioavailability (90.1% of fasted state).

Suggest total daily dose should be divided into four equal doses of carbamazepine suspension

and diluted with equal amount of diluent. Monitor carbamazepine

levels.


17-21

Carbidopa/ Levodopa

See Sinemet

Carvedilol

No data.

Decreased rate of absorption beyond jejunum site of

administration.

Rate of absorption is decreased however, bioavailability remains

unchanged



22-24

Cephalexin Concentration of cephalexin

with enteral nutrition is reduced to 90%.

Food has no effect on bioavailability or AUC. Food delays absorption.


(Class IIba, Level of Evidence C)

25,26


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Reference

Ciprofloxacin

Increased Tmax, while decreasing Cmax and

bioavailability. Enteral feeds have sufficient concentrations

of Calcium, Aluminum, Magnesium, and Zinc, to

chelate drug and decrease absorption.

Absorption decreased if given thru a jejunostomy tube as opposed to a gastrostomy tube due to the site of drug

absorption.

Food decreases bioavailability (31-82% of fasting state).

Severe infection: Recommend change to IV formulation.

(Class I, Level of Evidence B)

Mild-to-moderate infections: Suggest administering higher doses, 750mg twice a day. No dose adjustment needed for urinary tract infections due to drug concentrating at site of infection.. If administering

through a tube ending in the jejunum, therapeutic levels may not be achieved; in this case,

suggest administering IV or using another enteral route, if available. When using feeding tubes, use

crushed tablets as the suspension form cannot be used

with any feeding tube.


27-31


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Reference

Clindamycin No data available. Food has no effect on bioavailability

or absorption.



32

Clonidine No data No interactions



33

Clopidogrel

No data

Two fold increase in AUC with NG tube administration

No interaction


(Class IIb. Level of Evidence C)

34,35

Cyclosporine No data available.

High-fat meals (45 g fat) within 0.5 hour of a dose decreased AUC 13% and decreased Cmax 33%; effects of low-fat meals (15 g fat) were similar.

Suggest no dose adjustment required. Monitor cyclosporine

levels.


36

Dabigatran No data available

A high-fat meal delays the time to Cmax by approximately 2 hours but has no effect on the bioavailability.

The oral bioavailability of dabigatran increases by 75% if the pellets are

taken without the capsule shell compared to the intact capsule

formulation.

The capsules should not be broken or opened, so suggest

using another form of anticoagulation be administered

until patient is able to take capsule whole.

(Class III, Level of Evidence A)

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Dantrolene

No data.

Administration via NG tube without food resulted in

clinically effect 30 minutes after administration.

No data

Suggest no dosing adjustment required


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Reference

Diazepam

Commercially available diazepam solution has a

significantly lower bioavailability due to binding

with NG tubing.

Food has a minimal effect on bioavailability.

Suggest using diazepam tablets instead of solution.

(Class IIa, Level of Evidence C)

39,40

Diltiazem No data available.

Food increases absorption by 28% (increased maximal plasma

concentrations 73 +/- 19 ng/mL vs 130 +/- 82 ng/mL in the fasting and

nonfasting states, respectively). Co- administration of the tablets with high-

fat meals does not affect systemic exposure.

Suggest administering same total daily dose, but use immediate

release tablets dosed every 6-8 hours.


41,42

Divalproex / Valproic Acid

See Valproic Acid / Divalproex

Fluconazole

The mean AUC of fluconazole in serum after enteral administration with

concomitant enteral feeds did not significantly differ from IV.

The concentrations of fluconazole reached via

enteral administration were lower than those in serum for IV, but adequate to treat most

cases of deep mycoses.

Minimal food effect on bioavailability.



43-45

Gabapentin No data available AUC and Cmax increases by 14% with

food administration

Suggest no dose or tube feed adjustments required


46,47


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Reference

Hydralazine

Oral hydralazine given with a 6 hour infusion of Ensure via

NGT resulted in a 16% increased AUC and 30%

increased Cmax compared to fasting. The same 470 ml Ensure given as an enteral bolus, reduced the AUC by 62% and decreased Cmax by 87% as compared to fasting

states.

Studies have demonstrated inconsistent (increased, unchanged, and decreased) bioavailability of oral

hydralazine when given with food.

Suggest no dose adjustment..


21,48

Itraconazole No data available.

Capsule formulation is maximally absorbed when administered with

food and in the presence of normal gastric acidity Commercially available

oral liquid is maximally absorbed when administered in a fasting state.

Itraconazole oral solution was compared to capsules given to healthy volunteers under fed

conditions. The AUC for the solution was 149+68% of that obtained for the

capsule.

Suggest administration of the oral solution in patients who are receiving enteral feedings. . Suggest holding tube feeds 1 hour before and 1 hour after

administration. Monitor itraconazole levels.


49

Lacosamide No data Rate and extent of absorption not

affected by food



50

Lamotrigine No data No interactions



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Reference

Lanthanum Report of using lanthanum

successfully through an NGT with enteral nutrition.

Therapeutic effect of drug requires that it be taken with food.

Suggest scheduling 4-6 times per day for maximum effect. If a

combination of phosphate binders is needed, they should be

scheduled at different times.


52

Levetiracetam

The overall rate and extent of absorption of levetiracetam

was not significantly impaired after mixing the tablet with

enteral nutrition. Cmax may be slightly reduced after mixing, although the difference was

not significant when compared to control.

The overall rate and extent of absorption of oral levetiracetam was

not significantly impaired when mixing with food.


(Class IIb, Level of Evidence B)

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Reference

Levofloxacin No data available.

Oral administration of levofloxacin tablets with food prolongs the Tmax

by 1 hour and decreases the Cmax by 14% (not deemed clinically

significant). When levofloxacin solution was given with food, Cmax is

decreased approximately 25%.

Severe Infection: Suggest changing to IV formulation based

on ciprofloxacin data.


Mild-to-moderate infection: Suggest no change in dosing if

using TABLET. Suggest holding tube feedings 1 hour before and 1

hour after SOLUTION administration. If administering

through a tube ending in the jejunum, based on ciprofloxacin data, therapeutic levels may not

be achieved; in this case, suggest administering IV or using another

enteral route, if available.


54

Levothyroxine Sodium

Decreased levels as levothyroxine may bind to

enteral feeding tubes and/or may be lost during crushing

and transfer.

Food may decrease absorption and may increase fecal elimination.

For use < 7 days: Suggest no dose adjustment required.


For use > 7 days: Suggest holding tube feedings 1 hour pre

and post dose. Monitor thyroid function weekly.


55,56


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Reference

Linezolid

Linezolid oral suspension is rapidly and completely

absorbed via the enteral route. Bioavailability of

linezolid remains unaltered in the presence of continuous

enteral feedings.

Linezolid after Roux-en-y gastric bypass surgery results in an ~86% increase in AUC than patients prior to bypass.

This increase in AUC was associated with a decrease in

total body weight.

High fat meal may delay Tmax (from 1.5 to 2.2 hours) and decrease Cmax

by 17%. AUC remains relatively unaffected.



57,58

Lithium No data High amounts of caffeine increase

clearance. Food may increase therapeutic levels



59,60

Lorazepam No data available. No interactions.



61

Metoprolol No data available. Medication should be taken with food

or directly following meals.



62


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Reference

Metronidazole No data available. No interactions



63

Moxifloxacin

A single dose of moxifloxacin 400mg was given to healthy

volunteers in a crossover fashion. Moxifloxacin AUC

was slightly decreased when given with enteral nutrition

through an NGT compared to oral dosing. The difference was not deemed clinically

significant.

Moxifloxacin after Roux-en-y gastric bypass surgery results in ~25% reduction in Cmax and an absolute bioavailability of

~88%. These values are higher than those found in

patients without gastric bypass.

Moxifloxacin 400 mg has demonstrated bioequivalance with

respect to Cmax and AUC when given in fasting and fed states. Tmax is also

similar between fed and fasted conditions. High fat food may delay

rate of absorption; however, the extent of absorption is unaffected.

Suggest no dose adjustment required. May be given without respect to site of enteral tube.


64-66

Mycophenolate Mofetil

No data available.

Food has no effect on mycophenolic acid AUC, but has been shown to

decrease mycophenolic acid Cmax by 40%. Administration with iron has no

change in the AUC.

Suggest no dose adjustment required. Do not manipulate

tablets/capsules due to teratogenic effect, use

SUSPENSION.


67,68


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Reference

Mycophenolate Sodium

No data available. No interactions.

Do not use mycophenolate sodium tablets since theyshould not be crushed, chewed, or cut

due to teratogenic risk. . Convert to mycophenolate mofetil solution based on therapeutic interchange

protocol. (Class III, Level of Evidence C)

69

Nimodipine

No data available.

Holding tube feeds before and after the frequent

administration required for nimodipine would

dramatically decrease daily enteral intake.

Food decreases bioavailability by 38% and lowers peak plasma

concentration by 68%, compared to fasting. Bioavailability with food is 9% compared to 13% while fasting.



70

Oseltamivir

The median and trough plasma concentrations of the

active metabolite of oseltamivir given via a NGT or NJT tube with or without

enteral feedings, were similar or higher than ambulatory

patients. There was a delay in absorption in the NGT /

NJT group, but the AUC for the metabolite was similar to

ambulatory patients.

Coadministration with food had no significant effect on the peak plasma

concentration (551 ng/ml under fasted conditions and 441 ng/ml

under fed conditions) and the AUC (6218 ng h/ml under fasted conditions

and 6069 ng h/ml under fed conditions) of the active metabolite.


(Class iia, Level of Evidence B)

71,72

Oxcarbazepine No data Food does not affect bioavailability



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Reference

Oxycodone No data available. No interactions.



74

Pantoprazole

Crushing the delayed-release tablet can result in tube clogging. Dissolving the

enteric-coated granules in water prior to administration can destroy the medication

before it reaches its absorption site in the small

intestine. This is avoided by the compounded suspension.

Food has no effect on pantoprazole pharmacokinetics. Neither food nor antacids altered the bioavailability of pantoprazole. Tmax is highly variable and may increase when pantoprazole

is given with meals.

Suggest no dose adjustment required when using

compounded pantoprazole suspension.


Pantoprazole delayed-release and enteric-coated tablets should not be crushed for administration down gastric or jejunal feeding

tubes.

(Class III, Level of Evidence C)

75-77

Penicillin V Potassium

Unpredictable absorption with tube feeds.

Bioavailability may vary from 30 to 80%.

Reduces and prolongs peak serum level; extent of absorption

unchanged.

Suggest holding enteral nutrition 1 hour before and 2 hours after

dose (Class IIa, Level of Evidence B)

78


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Reference

Phenytoin

Feeding tubes may decrease absorption of

phenytoin suspension up to 80% via protein binding, poor

solubility, or binding to feeding tubes.

Food has no effect on the absorption

of brand-name Dilantin® or generic

phenytoin made by Teva. Food decreases the absorption of the

generic phenytoin made by Mylan.

Suggest using IV fosphenytoin or phenytoin; alternatively suggest

hold tube feeds 1 hour before and 1 hour after dose. Total daily

dose should be divided into twice daily dosing. Monitor phenytoin

levels.


79,80

UWHC Fosphenyt

oin and Phenytoin guideline

Posaconazole

Giving posaconazole with 240ml of a nutritional

supplement (Boost Plus) increased Cmax 3.4-3.5-fold and AUC 2.6-2.9-fold over the fasting state in healthy

volunteers.

Administering a single dose of posaconazole via an NGT

in healthy volunteers after 240ml of a nutritional

supplement (Boost Plus) resulted in 19% decrease in Cmax and ~24% decrease in

AUC compared to oral administration.

Giving posaconazole via NGT in surgical intensive

care unit patients receiving continuous enteral nutrition leads to inadequate plasma drug concentrations. The median fat intake was only 1.3 (range, 0-4.1) g/hour.

A 4-fold and 2.6-fold increase in Cmax and AUC was observed in subjects

given high-fat (~50g) and nonfat meals, respectively. A low-fat meal

(14g) resulted in a ~3-fold increase in Cmax and a 2.1-fold increase in AUC

as compared to fasting.

Canola oil (15mls) gives 15G of fat.

Suggest giving each posaconazole dose with 240ml of nutritional supplement or 15ml of canola oil. If patient is unable to tolerate supplement or canola oil, use alternative antifungal due to

inadequate posaconazole absorption.


81-85


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Reference

Quetiapine Administration via NGT

resulted in successful clinical effects

High fat meals increased AUC by 15% and increased Cmax 25%

Suggest dissolving tablet in water and no dosing adjustments.


86,87

Ranitidine

Greater than 90% of ranitidine tablets and syrup was recovered at 24 hours after mixing with 8 different

enteral feedings.

No interaction.

Suggest no dose adjustment necessary.


88,89

Rivaroxaban

No data available with enteral feedings

A 29% and 56% decrease in AUC and Cmax was reported

when rivaroxaban was released in the proximal

small intestine compared to the stomach. Exposure is

further reduced when drug is released in the distal small

intestine.

Doses up to 10 mg rivaroxaban had high oral bioavailability taking with or without food. Rivaoxaban 15 mg and 20 mg need to be taken with food to achieve high bioavailability (>=80%).

Suggest no dose adjustment required if enteral tube ends in

the stomach.


Recommend using alternative anticoagulant if enteral tube ends

distal to the stomach.

(Class III, level of evidence B)

90,91

Sevelamer

Manufacturer does not recommend administering

tablets through feeding tubes as contents expand in water and result in tube occlusion.

May use suspension formulation.

Therapeuticeffect of drug requires that it be taken with food.

Recommend change to suspension. Suggest scheduling 4-6 times per day for maximum

effect. If a combination ofphosphate binders is needed, they should be scheduled at

different times.


92,93


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Reference

Sinemet

No data available.

Jejunal administration does not affect bioavailability

Administration after food yielded varying peak to time effects ranging

30-360 minutes

Suggest not holding tube feeds. May increase dose for desired

effect.


94,95

Sirolimus No data available.

High-fat meals alter bioavailability of

oral Rapamune® solution. When

compared to fasting, a 34% decrease in Cmax, a 3.5-fold increase in Tmax, and a 35% increase in AUC was observed. After administration of

Rapamune® tablets with a high-fat

meal, Cmax, Tmax, and AUC showed increases of 65%, 32%, and 23%,

respectively. To minimize variability, the oral solution and tablets should be taken consistently with or without

food.

Suggest no dose adjustments.Monitor sirolimus

levels.


96

Sucralfate

Binds to protein in tube feedings. Insoluble

complexes form with tube feeding.

No activation due to alkaline pH of tube feeding.

Sucralfate may bind to the protein in food and reduce efficacy; therefore, it is recommended to give sucralfate 1 hour before or 2 hours after meals.

Use not recommended with enteral feedings.Alternative: use

PPI or H2RA.

(Class III, Level of Evidence C)

21,97

Tacrolimus

Enteral feedings through a nasojejunal feeding tube did not interfere with tacrolimus

capsule absorption.

Good bioavailability with food. High fat may decrease AUC and Cmax by

37% and 72%, respectively; Tmax was lengthened 5-fold.

High carbohydrate foods decreased mean AUC and mean Cmax by 28%

and 65%, respectively.


Monitor tacrolimus levels.


98,99


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Reference

Tamsulosin

No data available with enteral feedings.

Per company, capsule may be opened and the contents

administered in a small quantity of acidic fruit juice

(e.g. orange, grape)

Food decreases AUC ~30% and decreases Cmax ~40-70%.

Suggest holding tube feedings 1 hour predose. Open capsule and administer contents in acidic fruit

juice.


100

Theophylline

Absorption decreases by >30% when given with

enteral nutrition have been reported. Absorption of an

extended-release preparation with enteral feedings given

orally did not differ from absorption when

administered on an empty stomach.

Food does not cause clinically significant changes in absorption from

immediate-release dosage forms.

Suggest holding enteral nutrition 1 hour before and 1 hour after

dose.Use rapid release theophyline products/solutions. Take total daily dose and divide

into 3-4 doses per day.

Monitor theophylline levels.


2,101,102

Topiramate No data No clinical significance when mixed

with food



103

Valacyclovir No data available. No interactions.



104,105


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Reference

Valganciclovir No data available.

Food enhances bioavailability of valganciclovir HCl. AUC and Cmax

increase by 30% and 14% respectively, in the fed state.

Valganciclovir should be administered with food.



106,107

Valproic acid / Divalproex

No data available.

Administration with food may delay the rate of absorption, but does not alter systemic exposure. Difference

should be of minor clinical importance under steady state conditions.

Suggest administering same total daily dose, but use valproic acid solution dosed every 6-8 hours.

Monitor valproate levels.


108

Vancomycin No data available. No interactions.



109

Voriconazole

Crushed voriconazole tablets delivered via a NGT (enteral feeding interrupted only for

duration of dose administration) was

associated with adequate plasma levels in 88% of

study patients.

Infectious disease physicians concerned with inadequate

levels when given concurrently with enteral nutrition and would prefer

that enteral nutrition be held around dose.

Bioavailability of twice-daily 200mg voriconazole is reduced by ~22% as

measured by AUC after multiple dosing when taken with food as

compared to fasting.

Suggest holding tube feeds 1 hour before and 1 hour after

administration.

Monitor voriconazole levels. (Class IIb, Level of Evidence C)

110,111


23



access



Reference

Warfarin

Possible sequestering of warfarin in the

macromolecular fraction of the formulas. Current enteral

formulations have minimal amounts of Vitamin K to

interact with warfarin. Proteins in formula may bind

to warfarin.

No interactions.

Suggest no dose adjustment. Alternatively, suggest holding

feeds 1 hour before and 1 hour after administration. Either method requires close INR monitoring. Avoid formulas

containing soy protein. (Class IIb, Level of Evidence B)

21,112-

115

Zonisamide No data Food delays time to Cmax, however

bioavailability is unchanged



116

Abbreviations: AUC: Area under the curve; Cmax: Intravenous maximum concentration; H2RA: Histamine-2 receptor antagonists; INR: International Normalized Ratio; IV: Intravenous; NGT: Nasogastric tube; NJT: Nasojejunal tube; PPI: Proton pump inhibitor; Tmax: Time to maximum concentration


24

UW Health Implementation Benefits/Harms of Implementation 1. Appropriately dosing medications in patients receiving enteral nutrition will improve

patient outcomes.2. Standardizing dosing of medications in patients receiving enteral nutrition will provide

consistency in patient treatment.

Implementation Strategy – The guideline will be posted electronically.

Implementation Tools/Plan – Education: Information will be sent to nurses, pharmacists and physicians regarding the updated guideline.

Disclaimer This Clinical Practice Guideline provides an evidence-based approach for the dosing of medications in patients receiving continuous enteral feedings. It is understood that occasionally patients will not match the conditions considered in the guideline.


25

Appendix A. Evidence Grading Schemes

Table 2. Evidence Grading system of the American Society for Parenteral and Enteral Nutrition (ASPEN)

1

The evidence supporting each statement is classified as follows:

Class A There is good research-based evidence to support the guideline (prospective, randomized trials).

Class B There is fair research-based evidence to support the guideline (well-designed studies without randomization).

Class C The guideline is based on expert opinion and editorial consensus

Figure 1. Quality of Evidence and Strength of Recommendation Grading Matrix4


26

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