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Medication Route Interchange - Pediatric - Inpatient

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1
Medication Route Interchange –
Pediatric – Inpatient
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY ........................................................................................................... 3
SCOPE ................................................................................................................................... 3
METHODOLOGY .................................................................................................................... 3
INTRODUCTION ..................................................................................................................... 4
RECOMMENDATIONS ............................................................................................................ 4
UW HEALTH IMPLEMENTATION ............................................................................................. 6
APPENDIX A. SUMMARY OF CLINICAL RECOMMENDATIONS .................................................. 8
APPENDIX B. EVIDENCE GRADING SCHEME .......................................................................... 12
REFERENCES ........................................................................................................................ 13
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2
Contact for Content:
Name: Lucas Schulz, BCPS (AQ-ID) - Pharmacy
Phone Number: (608) 890-8617
Email Address: lschulz2@uwhealth.org
Name: Meghann Voegeli, PharmD, MS - Pharmacy
Phone Number: (608) 890-6658
Email Address: mvoegeli@uwhealth.org
Contact for Changes:
Name: Philip Trapskin, PharmD, BCPS - Pharmacy
Phone Number: (608) 265-0341
Email Address: ptrapskin@uwhealth.org
Guideline Authors:
Randy Braun, PharmD – Pharmacy
Lucas Schulz, PharmD, BCPS (AQ-ID) – Pharmacy
Joshua Vanderloo, PharmD, BCPS – Pharmacy
Coordinating Team Members:
Monica Bogenschutz, PharmD, BCPS, BCPPS – Pharmacy
Amy Crawford, PharmD, BCPPS – Pharmacy
Jessica Poehls, PharmD, BCPPS – Pharmacy
Jill Strayer, PharmD, BCPS – Pharmacy
Review Individuals/Bodies:
Sheryl Henderson, MD, PhD – Pediatrics Infectious Disease, Pediatric Infectious Disease
Stewardship Director
Dan Sklansky, MD – Pediatrics Hospitalists
Committee Approvals/Dates:
Pharmacy & Therapeutics Committee: February 2017
Release Date: February 2017 | Next Review Date: February 2020
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Executive Summary
Guideline Overview
This purpose of this guideline is to identify medications clinically appropriate to automatically change the
route of administration based on bioavailability, safety, and efficacy data. This document provides criteria
for safe and effective change in route of medication administration for inpatients (between parenteral and
enteral and within the enteral route including administration via various feeding tubes).

Key Practice Recommendations
See Appendix A: Summary of Clinical Recommendations

Companion Documents
ξ Pharmacist Medication Route Interchange – Adult/Pediatric – Inpatient [14]
ξ UW Health Intravenous Administration of Formulary Medications – Pediatric/Neonatal –
Inpatient/Ambulatory Clinical Practice Guideline
Scope
Intended Users:
Pharmacists, nurses, advanced practice providers, physicians

Objective:The objective of this guideline is to identify criteria for safe, effective, and clinically appropriate
interchange of medication routes based on bioavailability, pharmacokinetic, and safety and efficacy data.

Target Population:
Pediatric inpatients older than 48 weeks post menstrual age, defined as gestational age plus postnatal
age.

Interventions and Practices Considered:
Providing the safest and most appropriate route of administration for medications included in this
guideline.

Major Outcomes Considered:
Medication orders with the appropriate route of administration
Methodology
Methods Used to Collect/Select the Evidence:
Electronic database searches (e.g., PUBMED) were conducted by the guideline authors and workgroup
members to collect evidence for review. Data and recommendations from existing institutional guidelines
within and external to UW Health were evaluated. Workgroup expert opinion and clinical experience were
also considered during discussions of the evidence.

Methods Used to Formulate the Recommendations:
The workgroup members arrived at consensus recommendations through discussion of the literature and
expert experience. All recommendations endorsed or developed by the guideline workgroup were
reviewed and approved by other stakeholders or committees.

Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Internally developed recommendations were evaluated by the guideline workgroup using an algorithm
adapted from the Grading of Recommendations Assessment, Development and Evaluation (GRADE)
methodology (see Appendix B: Evidence Grading Scheme).

Rating Scheme for the Strength of the Evidence/Recommendations:
See Appendix B for the rating scheme used within this document.


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4


Recognition of Potential Health Care Disparities:
No healthcare disparities identified in literature search
Introduction
The enteral route of medication administration is preferred over the intravenous route for improved safety,
increased patient comfort, and decreased cost.1 The intravenous route of medication administration is
classified as an independent risk factor for having an adverse drug event (ADE) and is considered a high-
risk activity due to the potential for error resulting from the multiple necessary complex steps.2,3,4 Studies
demonstrate that intravenous medication administration is associated with a 3% higher risk for ADE per
each medication administered and represents the highest risk for ADE over all other routes of
administration.3,5 The magnitude of harm resulting from these errors has also contributed to its high-risk
classification.3,4 Furthermore, enteral administration may reduce the risk of intravenous catheter related
infections, medication incompatibilities, medication errors, and thrombophlebitis.1,5-7 Increased costs,
increased length of stay, and significantly higher mortality (versus other medication errors) have all been
linked to intravenous administration of medications.8,9 Intravenous administration of medications should
be minimized whenever possible by encouraging conversions to oral route whenever possible.3 Enteral
medication is associated with decreased cost in comparison to intravenous medications and associated
lines, sets, and infusion pumps necessary for administration. Early interchange to oral medications has
been linked to shorter lengths of stay without clinical outcome compromise, independent of ADEs.10-13

Criteria for inclusion of medications in the guideline were high oral bioavailability and good enteral
tolerance.14 Medications were included in this guideline based upon clinical data confirming tolerability
and high oral bioavailability.
Recommendations
1. Parenteral to enteral
1.1. To initiate the parenteral to enteral interchange, which includes medications administered orally
or via feeding tubes, the medication must be listed in Table 1. In addition, the patient must meet
all inclusion criteria and have none of the exclusion criteria. Enteral doses shall be rounded to
standardized doses as clinically appropriate.
1.2. Inclusion Criteria (UW Health low quality evidence, strong recommendation)
1.2.1. Patient must have a diet order and be tolerating either a clear liquid or more advanced
diet or must be tolerating enteral tube feedings.10
1.2.2. For antibiotic route interchange, patient must be showing clinical improvement in
symptoms as well as exhibiting downtrends in fever height, fever spike occurrence, and
previously elevated white blood cell count. 14,15
1.2.3. For antibiotic route interchange, the availability of a palatable pediatric formulation13
1.3. Exclusion Criteria (UW Health low quality evidence, strong recommendation)
1.3.1. For antibiotic route interchange, patient has been receiving intravenous antibiotics for a
duration fewer then 48 hours.
1.3.2. Patient is strict NPO, unable to swallow and without feeding tube, refuses oral
medications, or requires continuous gastric suctioning.10
1.3.3. Severe vomiting or diarrhea has been documented within the past 24 hours or patient
has an acute condition that affects gastrointestinal absorption (e.g. gastrointestinal
obstruction or bleed, ileus, grade III or IV mucositis, gastrointestinal transit time too short
for absorption, malabsorption syndromes, partial/total removal of the stomach, or short
bowel syndrome).
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1.3.4. Patient is hemodynamically unstable according to Table 4 or on high-doses of
vasopressors in presence of shock.13
1.3.5. Patient requires continuous tube feedings that cannot be interrupted and patient requires
a medication known to bind to enteral nutrition formulas (e.g. ciprofloxacin).16
1.3.6. Patient with endocarditis, meningitis, brain abscess, orbital cellulitis, CNS infection,
osteomyelitis, endophthalmitis, bacteremia, ventriculoperitoneal shunt infection, fever
with neutropenia, or necrotizing enterocolitis that should be treated with intravenous
antibiotic therapy.15,16
1.3.6.1. Patient may initially require prolonged IV therapy, however, conversion to oral
therapy may be considered after discussion with attending team.

2. Enteral to parenteral
2.1. For a patient to be eligible for the enteral to parenteral interchange the medication must be listed
in Table 1 and the patient must meet all inclusion criteria and have none of the exclusion
criteria.
2.2. Inclusion Criteria (UW Health low quality evidence, strong recommendation)
2.2.1. Patient is unable to tolerate oral medications or has failed a swallow study and does not
have a feeding tube in place.10
2.2.2. Patient has an acute condition that affects gastrointestinal absorption (e.g.
gastrointestinal obstruction or bleed, ileus, grade III or IV mucositis, gastrointestinal
transit time too short for absorption, malabsorption syndromes, partial/total removal of
the stomach, or short bowel syndrome).16
2.2.3. Patient is nutritionally compromised and parenteral administration of medication is
clinically warranted to minimize the amount of time the enteral nutrition is interrupted (e.g.
phenytoin, fluoroquinolones, etc.).16
2.2.4. Patient has had an NPO order for greater than two days.10
2.2.5. Patient requires continuous gastric suctioning.16
2.3. Exclusion Criteria (UW Health low quality evidence, strong recommendation)
2.3.1. Acetaminophen, isavuconazole, posaconazole, and voriconazole cannot be converted
from enteral to parenteral formulation without a prescribing provider order.

3. Transdermal to Enteral
3.1. For a patient to be eligible for the transdermal to enteral interchange the medication must be
listed in Table 3 (transdermal) and the patients must meet all inclusion criteria and have none of
the exclusion criteria.
3.2. Inclusion Criteria (UW Health low quality evidence, strong recommendation)
3.2.1. Patient must have a diet order and be tolerating either a clear liquid or more advanced
diet or must be tolerating enteral tube feedings.10
3.2.2. An active medication order for the patient’s home transdermal dose must exist in Health
Link.
3.2.3. The transdermal form of the medication is a non-formulary item and the oral analogue
exists on the UW Health formulary.
3.3. Exclusion Criteria (UW Health low quality evidence, strong recommendation)
3.3.1. Patient is strict NPO, unable to swallow and without feeding tube, or refuses oral
medications.10
3.3.2. Severe vomiting or diarrhea has been documented within the past 24 hours or patient
has an acute condition that affects gastrointestinal absorption (e.g. gastrointestinal
obstruction or bleed, ileus, grade III or IV mucositis, gastrointestinal transit time too short
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for absorption, malabsorption syndromes, partial/total removal of the stomach, or short
bowel syndrome).16
3.3.3. Patient requires continuous tube feedings that cannot be interrupted and patient requires
a medication known to bind to enteral nutrition formulas16

4. Rectal to enteral
4.1. For a patient to be eligible for the rectal to enteral interchange the medication must be listed in
Table 2 and the patients must meet all inclusion criteria and have none of the exclusion criteria.
4.2. Inclusion Criteria (UW Health low quality evidence, strong recommendation)
4.2.1. Patient must have a diet order and be tolerating either a clear liquid or more advanced
diet or must be tolerating enteral tube feedings.10
4.3. Exclusion Criteria (UW Health low quality evidence, strong recommendation)
4.3.1. Patient is strict NPO, unable to swallow and without feeding tube, or refuses oral
medications.10
4.3.2. Severe vomiting has been documented within the past 24 hours or patient has an acute
condition that affects gastrointestinal absorption (i.e., gastrointestinal obstruction or
bleed, ileus, grade III or IV mucositis, gastrointestinal transit time too short for absorption,
malabsorption syndromes, partial/total removal of the stomach, or short bowel
syndrome).16
4.3.3. Patient requires continuous tube feedings that cannot be interrupted and patient requires
a medication known to bind to enteral nutrition formulas16

5. Documentation
5.1. Medication orders meeting the above criteria for the change in the route of administration are
subject to interchange as soon as the patient meets the established criteria.
5.2. Once a patient meets the criteria, the pharmacist discontinues the current medication order and
converts the medication to the appropriate corresponding dosage form by placing an order in the
EMR.
5.3. The pharmacist will communicate the route interchange by page to the patient’s primary service
provider on-call (e.g. intern physician, resident physician, advanced practice prescriber,
attending physician).
UW Health Implementation
Potential Benefits:
ξ Decreased length of stay
ξ Decreased cost of medication therapy
ξ Increased patient comfort
ξ Decreased risk associated with intravenous administration of medications (e.g. extravastation,
ADE associated with IV administration)

Potential Harms:
ξ No potential harms identified

Qualifying Statements: As new data becomes available for safety and efficacy of route administration of
medications recommendations may change.

Guideline Metrics
1. Guideline adherence

Implementation Plan/Clinical Tools
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1. Guideline will be posted on uConnect in a dedicated location for Clinical Practice Guidelines.
2. Release of the guideline will be advertised in the Physician/APP Briefing newsletter.
3. Content and hyperlinks within clinical tools, documents, or Health Link related to the guideline
recommendations (such as the following) will be reviewed for consistency and modified as
appropriate.

Delegation Protocols
ξ Pharmacist Medication Route Interchange – Adult/Pediatric – Inpatient [14]

Disclaimer
Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of
patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a
clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit
the clinical condition contemplated by a guideline and that a guideline will rarely establish the only
appropriate approach to a problem.


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Appendix A. Summary of Clinical Recommendations

Table 1. Medications Approved for Parenteral and Enteral Route Interchange
*See Lexi-Comp or Micromedex “Do not crush” list for applicability of crushing tablets
Parenteral regimen Parenteral dose/frequency Enteral dose/frequency Bioavailability Comments
Acetaminophen17,18
10 to 15 mg/kg/dose 10 to 15 mg/kg/dose
85-98% 1 to 1 dosing 500 mg 500 mg
1000 mg 1000 mg
Azithromycin17,18
10 mg/kg every 24 h 10 mg/kg every 24 h
37% to 38%
1 to 1 dosing
Extended release suspension (Zmax) is not
interchangeable with immediate-release
formulations
5 mg/kg every 24 h 5 mg/kg every 24 h
250 mg every 24 h 250 mg every 24 h
500 mg every 24 h 500 mg every 24 h
Ciprofloxacin1,14,19,20
10 mg/kg/dose every 12 h 15 mg/kg/dose every 12 h
60% to 80%
Extended release tablets and immediate
release formulations are not interchangeable.
Absorption decreased if given thru a
jejunostomy tube as opposed to a gastrostomy
tube due to the site of drug absorption. When
using feeding tubes, use crushed tablets as the
suspension form cannot be used with any
feeding tube. (UW Health moderate quality
evidence, weak/conditional recommendation)
10 mg/kg/dose every 8 h 20 mg/kg/dose every 12 h
15 mg/kg/dose every 12 h 20 mg/kg/dose every 12 h
200 mg every 24 h 250 mg every 24 h
200 mg every 12 h 250 mg every 12 h
400 mg every 24 h 500 mg every 24 h
400 mg every 12 h 500 mg every 12 h
400 mg every 8 h 750 mg every 12 h
Clindamycin17,18
20 mg/kg/day divided every 6-8 h 20 mg/kg/day divided every 6-8 h
90% Maximum oral dose is 450 mg due to
tolerability
30 mg/kg/day divided every 6-8 h 30 mg/kg/day divided every 6-8 h
40 mg/kg/day divided every 6-8 h 40 mg/kg/day divided every 6-8 h
300 mg every 6-8 h 300 mg every 6-8 h
600 mg every 6-8 h 450 mg every 6-8 h
Diphenhydramine17,18
0.25-1 mg/kg/dose 0.25-1 mg/kg/dose
65% to 100%
1 to 1 dosing
Maximum single dose: 50 mg
Oral solution has a higher bioavailability than
capsules
6.25 mg 6.25 mg
12.5 mg 12.5 mg
25 mg 25 mg
Doxycycline2,17,18
2-4 mg/kg/day divided every 12-24 h 2-4 mg/kg/day divided every 12-24 h Virtually
completely
absorbed
1 to 1 dosing
No enteral solution available, only interchange
to available enteral doses within 10% of
intravenous dose 100 mg every 12 h 100 mg every 12h
Fluconazole14,17,18
3-12 mg/kg/dose 3-12 mg/kg/dose
>90% 1 to 1 dosing
100 mg every 12 h 100 mg every 12h
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Parenteral regimen Parenteral dose/frequency Enteral dose/frequency Bioavailability Comments
100 mg 100 mg
200 mg 200 mg
400 mg 400 mg
Folic acid17,18
100 mcg/day 100 mcg/day
76% to 93% 1 to 1 dosing 200 mcg/day 200 mcg/day
300 mcg/day 300 mcg/day
400 mcg/day 400 mcg/day
Lacosamide17,18 1-15 mg/kg/day divided twice daily 1-15 mg/kg/day divided twice daily 100% 1 to 1 dosing
50-200 mg 50-200 mg
Levocarnitine17,18 20-100 mg/kg/day IV *See comments 15-16%**
*When appropriate, patient may be converted
to prior enteral home regimen
**mucosal absorption may be saturated at
doses >2 grams
Levothyroxine14,20-22
15 mcg/day 25 mcg/day
capsule: 40-
80%
tablet: 48-80%
Parenteral dose should be approximately 80%
of enteral dose. The relative bioavailability of
the oral capsule is approximately 103%
compared to the tablet. When appropriate,
patient may be converted to prior enteral home
regimen
35 mcg/day 50 mcg/day
50 mcg/day 75 mcg/day
75 mcg/day 100 mcg/day
85 mcg/day 125 mcg/day
100 mcg/day 150 mcg/day
125 mcg/day 175 mcg/day
150 mcg/day 200 mcg/day
Levetiracetam14,17,18
7-50 mg/kg/dose 7-50 mg/kg/dose
100% 1 to 1 dosing 500 mg 500 mg
1000 mg 1000 mg
Levofloxacin17,18
5 to 10 mg/kg/dose 5 to 10 mg/kg/dose
99% 1 to 1 dosing 250 mg 250 mg
500 mg 500 mg
750 mg 750 mg
Linezolid14,17,18
10 mg/kg/dose every 8 h 10 mg/kg/dose every 8 h
100% 1 to 1 dosing
600 mg every 12 h 600 mg every 12 h
Metronidazole17,18
30 to 40 mg/kg/day divided every 6-8 h 30 to 40 mg/kg/day divided every 6-8 h
100% 1 to 1 dosing 100 mg 100 mg
500 mg 500 mg
Moxifloxacin2,17,18 10 mg/kg/dose 10 mg/kg/dose 90% 1 to 1 dosing No enteral solution available, only interchange
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Parenteral regimen Parenteral dose/frequency Enteral dose/frequency Bioavailability Comments
400 mg 400 mg to available enteral doses within 1% of
intravenous dose
Pantoprazole14,17,18
< 5 yo:
0.5-1 mg/kg/dose every 12-24 h
< 5 yo:
0.5-1 mg/kg/dose every 12-24 h
77% 1 to 1 dosing
> 5 yo:
20-40 mg once daily
> 5 yo:
20-40 mg once daily
Ranitidine17,18
2 to 4 mg/kg/day IV divided every 6-8 h 4 to 8 mg/kg/day enterally divided twice daily
48%
50 mg IV every 8 h 150 mg enterally twice daily
Rifampin17,18 10 to 20 mg/kg/day 10 to 20 mg/kg/day 90 to 95% 1 to 1 dosing
600 mg 600 mg
Sulfamethoxazole-
Trimethoprim17,18
6-20 mg TMP/kg/day divided every 6-12 h 6-20 mg TMP/kg/day divided every 6-12 h
90 to 100% 1 to 1 dosing Dosed by trimethoprim component 80 mg 80 mg
160 mg 160 mg
Thiamine17,18
200 mcg/day 200 mcg/day
5.3% 1 to 1 dosing 500 mcg/day 500 mcg/day
1000 mcg/day 1000 mcg/day
Valproic Acid17,18 10-15mg/kg/day divided q6h 10-15mg/kg/day in divided doses* 90%
Total daily IV dose is equivalent to the total
daily oral dose; however, IV dose should be
divided with a frequency of every 6 hours.
Conversion from oral Depakote IR to ER may
require a total daily dose increase of 8-20%.
*When appropriate, patient may be converted
to prior enteral home regimen



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11


Table 2. Guidance for Rectal and Enteral Route Interchange

Rectal regimen Rectal dose/frequency Enteral regimen Enteral dose/frequency Bioavailability Comments
Acetaminophen
Suppository17,23 10 to 20 mg/kg/dose every 4 to 6 h Acetaminophen 10 to 15 mg/kg/dose every 4 to 6 h 80% Max: 75 mg/kg/day





Table 3. Guidance for Transdermal and Enteral Route Interchange

Transdermal regimen Transdermal dose/frequency Enteral regimen Enteral dose/frequency Bioavailability Comments
Methylphenidate Patch
(Daytrana)17,18,24
Patch Size(cm^2):
Methylphenidate IR

Oral:
22% (d-
methylphenidate),
5% (l-
methylphenidate)
The manufacturer recommends
patients converting from another
formulation of methylphenidate to
the transdermal patch should be
initiated at 10 mg regardless of
their previous dose and titrated as
needed due to the differences in
bioavailability of the transdermal
formulation
12.5 (10 mg/9 h) 5 mg enterally 3 times daily
18.75 (15 mg/9 h) 7.5 mg enterally 3 times daily
25 (20 mg/9 h) 10 mg enterally 3 times daily
37.5 (30 mg/9 h) 15 mg enterally 3 times daily
Oxybutynin Patch17,18 3.9 mg/day patch every 3-4 days Oxybutynin IR 0.1 to 0.2 mg/kg/dose enterally up to
5 mg 2-3 times daily Oral: 6%


Table 4. Pediatric Unstable Vital Signs

Age Respiratory Rate Heart Rate Systolic Blood Pressure
0-6 months <40 or >60 >180 <70
6-24 months <25 or >50 >160 <72
3-7 years <20 or >30 >140 <76
7-10 years <10 or >30 >120 <84
11-17 years <10 or >30 >120 <90

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12


Appendix B. Evidence Grading Scheme

Figure 1. GRADE Methodology adapted by UW Health


GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate We are quite confident that the effect in the study is close to the true effect, but it
is also possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.

GRADE Ratings for Recommendations For or Against Practice
Strong The net benefit of the treatment is clear, patient values and circumstances
are unlikely to affect the decision.
Weak/conditional
Recommendation may be conditional upon patient values and
preferences, the resources available, or the setting in which the
intervention will be implemented.


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13


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