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Intranasal Medication Administration - Adult/Pediatric - Inpatient/Ambulatory

Intranasal Medication Administration - Adult/Pediatric - Inpatient/Ambulatory - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Medications


Intranasal Medication Administration – Adult/Pediatric –
Inpatient/Ambulatory/Primary Care Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
Executive Summary ................................................................................................................................ 3
Scope ..................................................................................................................................................... 7
Methodology ......................................................................................................................................... 7
Definitions ............................................................................................................................................. 8
Introduction ........................................................................................................................................... 8
Recommendations ................................................................................................................................. 9
General Recommendations for Intranasal Administration ....................................................................... 9
Drug-Specific Practice Recommendations ............................................................................................. 10
UW Health Implementation ................................................................................................................. 14
Appendix A. Evidence Grading Scheme ................................................................................................. 15
References ........................................................................................................................................... 17
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2
Contact for Content:
Philip Trapskin, PharmD, BCPS
608- 263 -1328
ptrapskin@uwhealth.org
Contact for Changes:
Philip Trapskin, PharmD, BCPS
608- 263 -1328
ptrapskin@uwhealth.org
Guideline Author:
Ashlinn Samuel, PharmD
Joshua Vanderloo, PharmD, BCPS
Coordinating Team Members:
Cindy Gaston, PharmD
Aaron Steffenhagen, PharmD, BCPS
Joe Halfpap, PharmD, BCPS
Review Individuals/Bodies:
Michael K. Kim, MD; Gregory A. Hollman, MD; Brian LaRowe, RPh, MSc;
Peggy Riley, RN, MN, MPH
Committee Approvals/Dates:
P&T Committee – February 2017
Release Date: February 2017 Next schedule review: February 2019
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Executive Summary
Guideline Overview
This clinical practice guideline is intended to guide clinicians in the use of medications intranasally for
systemic effect which are not labelled for intranasal use.

Key Revisions (2016 Periodic Review)
None

Key Practice Recommendations
Refer to Table 1.


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Table 1. Intranasal medication administration for systemic absorption.
Drug Appropriate
Indications Preferred Product Dosing Pharmacokinetics
Adverse Effects Related to
Intranasal Administration
Dexmedetomidine
Premedication
prior to general
anesthesia and
procedural
sedation for minor
surgeries and
procedures1-10
Dexmedetomidine
HCl 100 mcg/mL
intranasal solution
[785204]
Adult:
1-1.5 mcg/kg 45 -60 minutes prior to
surgery or procedure requiring
sedation15,17 ,23

Pediatric (≥10 kg and ≥1 year old):
1-2 mcg/kg 45 -60 minutes prior to
surgery or procedure requiring
sedation; use 1 mcg/kg for
procedures of anticipated duration
<45 minutes 1,3 ,5-9
Bioavailability: 65% (range: 35 -
93%)
4

Onset: 30 -45 minutes (range: 25 -68
minutes) 2,4 ,7 -10
Peak effect: 90 -105 minutes (in
adults) 10
Duration of action:
 Adult: Easily arousable sedation
with 1-1.5 mcg/kg dose for ≥180
minutes10
 Pediatric: Dose dependent; 1
mcg/kg dose 45 minutes (range:
40 -100 minutes) 1,7 ,8 and 2
mcg/kg dose 95 minutes (range:
45 -135 minutes) 7
None specific to intranasal route of
administration1-10
Fentanyl Acute analgesia
Fentanyl citrate 50
mcg/mL intranasal
solution [785209]
Adult:
0.9 -2.2 mcg/kg (maximum of 100
mcg/2 mL) initial dose, may repeat
with 60 mcg every 5 minutes
thereafter24 ,25

Pediatric (≥10 kg and ≥1 year old):
1-1.5 mcg/kg/dose 11-17
Bioavailability: 55-77% 18
Onset: 5 to 10 minutes15,16 ,18
Peak effect: ~20 m inutes18
Duration of action: ~50 minutes 18
Self -resolving unpalatable taste,
watery eyes, nasal congestion, or
throat irritation in adult patients
(information regarding pediatric
adverse effects not available) 15,19
Flumazenil
Initial route of
administration for
cases of
suspected or
actual
benzodiazepine
overdose when IV
route is not
available 96 ,97
Flumazenil 100
mcg/mL intranasal
solution [785205]
Adult:
Not recommended

Pediatric:
40 mcg/kg with a maximum dose of
200 mcg (100 mcg in each nostril) 20,21
Bioavailability: Undetermined21
Onset: <2 minutes 21
Peak effect: 2 minutes21
Duration of action: Undetermined21
None specific to int ranasal route of
administration20,21
Glucagon Not recommended for intranasal use22-33
Haloperidol Not recommended for intranasal use
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Drug Appropriate
Indications Preferred Product Dosing Pharmacokinetics
Adverse Effects Related to
Intranasal Administration
Hydromorphone Acute analgesia
Hydromorphone
HCl 1 mg/mL
intranasal solution
[785206]
Adult:
1-2 mg per dose 34 -36

Pediatric:
Not recommended 34 -36
Bioavailability: ~55% (1 mg dose
range 26 -71%; 2 mg dose range 36 -
78%)
36

Onset: 10-20 minutes34 ,35
Peak effect: 20-50 minutes 34 ,35
Duration of action: 180 minutes 3 5
Self -resolving unpalatable taste,
nasal itching, nasal congestion, or
nasal stinging34 ,35
Ketamine
Procedural
sedation and
premedication for
reducing
preoperative
anxiety 37 -49
Ketamine HCl 100
mg/mL intranasal
solution [785203]
Adult:
Not recommended 37 -49

Pediatric (≥5 kg and ≥6 months
old):
 Procedural sedation: 6 -9 mg/kg
4 -8 minutes prior to procedures
anticipated to last <30 -40
minutes37 ,38 ,48
 Premedication: 0.5 -10 mg/kg
(preference of doses ≥3 mg/kg)
15-30 minutes prior to separation
from parents 40 -44 ,49 ,50
Bioavailability: 50% 44
Onset: ~5 minutes (range: 4 -10
minutes) 37 ,38 ,48
Peak effect: Not established 37 -39 ,48 ,49
Duration of action: 40 minutes
(range: 22 -69 minutes) 37 -39 ,48 ,49
None specific to intranasal route of
administration 37 -49
Lidocaine
Treatment of
moderate to
severe migraines
when alternatives
are ineffective and
for idiopathic
second-division
trigeminal
neuralgia51-55
Lidocaine HCl 40
mg/mL (4%)
intranasal solution
[785202]
Adult:
 Migraines: 20 mg in nostril of
affected side if unilateral, 20 mg
in each nostril if bilateral; may
repeat with second dose if lack of
relief within 2-15 minutes51-54
 Idiopathic second-division
trigeminal neuralgia: 8 mg in
each nostril for a total dose of 16
mg55

Pediatric:
Not recommended 51-55
Bioavailability: 26% (range: 5 -
48%)
56

Onset: 5-15 minutes51
Peak effect: Undetermined
Duration of action: Undetermined
Self -resolving local irritation (burni ng,
stinging, numbness), bitter taste,
numbness of the throat, and nausea 51
Lorazepam Acute seizure
treatment
Lorazepam 4
mg/mL injection
solution
Adult:
0.1 mg/kg 55,57

Pediatric (≥2 months old):
0.1 mg/kg (consider maximum of 4
mg dose) 57 ,58
Bioavailability: ~7 8 % 59
Onset: ~5 minutes (range: 1 -25
minutes) 57 ,58
Peak effect: 30 -105 minutes59 ,60
Duration of action: ~60 minutes 58
Poor taste, cool feeling in nose and
throat, burning nasal sensation 55,57
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Drug Appropriate
Indications Preferred Product Dosing Pharmacokinetics
Adverse Effects Related to
Intranasal Administration
Midazolam
Procedural
sedation prior to
minor procedures
or imaging and
pre-induction for
general anesthesia
and alternative
therapy for
pediatric seizures
when the IV route
is not available
61 ,62

Midazolam HCl 5
mg/mL intranasal
solution [785196]
Adult:
Not routinely recommended due to
nasal volume limitations, but may
consider 0.2-0.3 mg/kg if alternative
routes unavailable (maximum of 10
mg due to volume administration
limitations) 63

Pediatric:
 Procedural sedation and pre -
induction for general anesthesia:
0.2-0.5 mg/kg (consider
maximum dose of 10 mg due to
volume limitations) 50,61 ,62 ,64 -82
 Seizures: 0.2 -0.5 mg/kg 63 ,83 -89 ;
Reference Status Epilep ticus -
Pediatric - Emergency
Department/Inpatient Clinical
Practice Guideline for additional
information
Bioavailability: 50-83% 64
Onset: Average 3 -15 minutes (range:
0.5 to 19 minutes) 64 ,67 ,68 ,73 ,83 ,86 ,88
Peak effect: ~25 minutes (10 -48
minutes) 90 ,91
Duration of action: 21 to 60 minutes
(dose -dependent) 61 ,64 ,67 ,73 ,79 ,92
Self -limiting discomfort, irritation, or
burning sensation in nasal
passages 60 ,90
Morphine Not recommended for intranasal use93-97
Naloxone
Initial route of
administration for
cases of
suspected or
actual opioid
overdose when the
IV route is not
available
Naloxone 1 mg/mL
intranasal solution
[785210]
Adult:
2 mg (1 mg in each nostril) 98 -104

Pediatric:
0.4 mg total dose (0.2 mg in each
nostril) based upon a single case
report20
Bioavailability: 4% 105
Onset: Undetermined105
Peak effect: 6 -9 minutes 105
Duration of action: Undetermined105
None specific to intranasal route of
administration 98 -108
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7

Companion Documents
ξ UWHC Clinical Policy 8.76: Pain Management
ξ UWHC Clinical Policy 8.38: Adult Sedation Policy
ξ UWHC Clinical Policy 8.56: Pediatric Sedation Policy
ξ UWHC Sedation Nursing Practice Guideline
ξ Pain Care Fast Facts: Intranasal Analgesia Prior to Insertion of Nasogastric Tube – Pediatric
ξ Pain Care Fast Facts: Intranasal Analgesia Prior to Insertion of Nasogastric Tube – Adult
ξ Status Epilepticus - Pediatric - Emergency Department/Inpatient Clinical Practice Guideline

Scope
Disease Condition: Off-label intranasal medication administration

Clinical Specialty: All medical specialties

Intended Users: Physicians, Advanced Practice Providers, Nurses, and Pharmacists

Objective
The clinical practice guideline is intended to provide a standardized process for off-label intranasal
administration of specific medications which are not commercially intended for administration via this route
and which have demonstrated systemic absorption and effects.

For information regarding intranasal analgesia prior to insertion of nasogastric tubes, please see the
following guidance documents: Pain Care Fast Facts: Intranasal Analgesia Prior to Insertion of Nasogastric
Tube – Pediatric and Pain Care Fast Facts: Intranasal Analgesia Prior to Insertion of Nasogastric Tube –
Adult.

Target Population
Adult and pediatric patients for whom off-label intranasal mediations are being considered.

Interventions and Practices Considered
This guideline recommends intranasal medication dosing, product selection, and other considerations for
the use of medications given intranasally which are not labeled for intranasal use.

Major Outcomes Considered
ξ Utilization of intranasal medications as identified in guideline
ξ Adverse events associated with intranasal medication use

Methodology
Methods Used to Collect/Select the Evidence
Electronic database searches (i.e. PUBMED) were conducted and workgroup members to collect evidence
for review; for the 2016 revision, clinical evidence dating back to January 2014 was reviewed. Additionally,
hand searches were performed within selected evidence for other relevant resources. Expert opinion,
clinical experience, and regard for patient safety/experience were also considered during discussions of
the evidence.

PubMed was used as the primary modality for identifying primary literature articles. The Boolean search
string used for each drug was “[generic drug name without specifics about salts/chemical formulation] AND
(nasal OR intranasal)”. For example, the search string for fentanyl was “fentanyl AND (nasal OR
intranasal)”. All clinical and pharmacokinetic case reports and trials in human patients where the drug was
used via the intranasal route were included, and all animal studies were excluded. A comprehensive
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8

search was performed by reviewing the references of all included studies for more studies which should be
considered in guideline development.

Methods Used to Formulate the Recommendations
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, or those adopted from external sources without an assigned
evidence grade, were evaluated by the guideline workgroup a modified Grading of Recommendations
Assessment, Development and Evaluation (GRADE) methodology. 109

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

Recognition of Potential Health Care Disparities
No potential disparities identified.

Definitions
LMA MAD Nasal TM : “mucosal atomization device” (MAD) made by the company LMA North America, Inc. which is
attached to a standard syringe via Luer-Lock in order to turn an intravenous drug product into a fine mist for intranasal
administration (See Figure 1).

Figure 1. LMA MAD Nasal™


Introduction
Intranasal (IN) administration of medications has previously demonstrated advantages in effectiveness, patient
comfort, and workplace safety when compared to alternative routes such as intravenous (IV) and intramuscular (IM)
for numerous medication classes including: opioid agonists, benzodiazepines (BZ Ds), anesthetics, sedatives, and
antidotes.110,111 Nasal administration is most commonly associated with local topical outcomes, but kinetic and clinical
trials have previously confirmed bioavailability which approximates that of IV or IM administration for numerous
systemic medications with IN administration. Therefore, the highly vascularized nasal mucosa can be considered an
effective modality for parenteral administration which provides rapid absorption and bypasses fir st-pass
metabolism. 112 IN administration may yield several advantages over other parenteral routes of administration, as it
circumvents pain associated with IV line placement and IM delivery. Additionally, IV access can be difficult, may
delay care, requires nursing time resources, and can be unnecessary in certain patient populations and conditions. 113


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Recommendations

General Recommendations for Intranasal (IN) Administration
1. Do not administer medications nasally if the patient’s nasal passages demonstrate signs of local mucosal irritation,
inflammation, bleeding, excoriation, or ulceration. 114 Consider an alternative route of administration.115 (UWHealth
Strong Recommendation, Very Low Quality of Evidence)
2. Administration volumes
2.1. Administration volumes should be minimized, as mucosal surfaces may become saturated leading to runoff
into the oropharynx and decreased absorption. 115 ( UWHealth Strong Recommendation, Moderate Quality of
Evidence)
2.2. Optimal volume of administration per nostril is between 0.15 mL and 0.4 mL in order to prevent oral
absorption, but up to 1 mL may be administered per nostril. 115-118 (UWHealth Strong Recommendation,
Moderate Quality of Evidence)
2.3. Repeat dosing has not been studied for most medications administered via the IN route and is not
recommended unless otherwise specified for a specific drug. (UWHealth Strong Recommendation, Low
Quality of Evidence)
2.4. Maximally concentrated drug products should be used whenever possible in order to reduce volume of
administration.115 (UWHealth Weak/Conditional Recommendation, Very Low Quality of Evidence)
3. Administration Technique (See Figure 2)
3.1. If able, have the patient gently blow his or her nose prior to administration. 114 (UWHealth Weak/Conditional
Recommendation, Very Low Quality of Evidence)
3.2. Draw appropriate volume of drug plus an additional 0.1 mL into a 1 mL or 3 mL syringe depending upon final
volume of drug required. The volume drawn up should be 0.1 mL more than the volume to be administered in
order to account for dead space in the LMA MAD Nasal. 11 (UWHealth Weak/Conditional Recommendation,
Very Low Quality of Evidence)
3.3. Remove needle and discard securely. Attach the LMA MAD Nasal to the syringe via the Luer-lock connector
on the syringe.
3.4. Routine IN administration without the LMA MAD Nasal is not recommended, as the MAD increases consistent
medication absorption. 115 (UWHealth Strong Recommendation, Very Low Quality of Evidence)
3.5. IN Delivery Device Placement and Considerations
3.5.1. Adults and adolescents: Use free hand to hold occiput of the patient’s head stable. Place tip of LMA
MAD Nasal snugly against the nostril and aim up and outward toward lateral nasal wall (the inferior
and middle turbine mucosa). 114 (UWHealth Weak/Conditional Recommendation, Very Low Quality of
Evidence)
3.5.2. Young pediatric patients: Show patients the “squirter” (LMA MAD Nasal) and reassure that the device
is not a “shot”. Consider allowing the child to touch and feel the soft “pillow” of the device so they
know it will not hurt them. It is encouraged for patients to sit on the parent or caregiver’s lap with the
parent or caregiver giving a hug over his or her arms (in a comfort hold) to prevent the child from
covering his or her face. Patients can be told to “sniff like smelling a flower” as the medication is
delivered. (UWHealth Weak/Conditional Recommendation, Very Low Quality of Evidence)
3.6. Briskly compressing the syringe plunger, deliver half of the medication dose into each nostril to maximize
dispersion and absorption surface area. 115 (UWHealth Strong Recommendation, Low Quality of Evidence)
3.7. Ideally, have the patient remain in a semirecumbent position with the head of the bed elevated 30-45 degrees
for 10 minutes after administration in order to prevent runoff out of the nose, if able. 114 (UWHealth
Weak/Conditional Recommendation, Very Low Quality of Evidence)
3.8. Instruct the patient to refrain from blowing his or her nose for at least 60 minutes after IN administration to
maximize medication absorption. 114 (UWHealth Strong Recommendation, Very Low Quality of Evidence)
4. Adverse Effects
4.1. The systemic adverse effects and patient monitoring associated with intravenous administration of the
medications included in this guideline also apply to IN administration. ( UWHealth Strong Recommendation,
Very Low Quality of Evidence)
4.2. Administration via the IN route has demonstrated self-limiting local adverse effects for several medications in
addition to the systemic adverse effects associated with alternative routes of administration. See Drug-
Specific Practice Recommendations for information regarding specific medication adverse effects.
(UWHealth Strong Recommendation, Very Low Quality of Evidence)
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Figure 2.LMA MAD™ Administration Technique (Adults and Adolescents)119



Drug-Specific Practice Recommendations

Dexmedetomidine
1. Appropriate indications: Premedication prior to general anesthesia and procedural sedation for minor surgeries
and procedures.1-10 (UWHealth Strong Recommendation, Moderate Quality of Evidence)
2. Dosing
2.1. Adult: 1-1.5 mcg/kg 45 to 60 minutes prior to surgery or procedure requiring sedation. 2,4,10 (UWHealth Strong
Recommendation, Moderate Quality of Evidence)
2.1.1. Use cautiously in patients over the age of 40 years due to limited evidence for IN administration in this
patient population.2,4 ,10 (UWHealth Weak/Conditional Recommendation, Very Low Quality of
Evidence)
2.1.2. Adjunct agents should be used to maintain adequate sedation for procedures lasting longer than 180
minutes.2 (UWHealth Weak/Conditional Recommendation, Very Low Quality of Evidence)
2.2. Pediatric (patients ≥10 kg and ≥1 year of age): 1-2 mcg/kg 45 to 60 minutes prior to surgery or procedure
requiring sedation. 1,3,5-9 (UWHealth Strong Recommendation, High Quality of Evidence)
2.2.1. For procedures of anticipated duration fewer than 45 minutes, patients should receive 1 mcg/kg
dexmedetomidine instead of 2 mcg/kg due to possible prolonged sedation and recovery time. 1,3,5,7
(UWHealth Strong Recommendation, High Quality of Evidence)
2.2.2. Adjunct agents may be necessary to maintain adequate sedation for procedures lasting longer than 95
minutes in patients who receive 2 mcg/kg. 7 (UWHealth Strong Recommendation, Low Quality of
Evidence)
2.2.3. Doses greater than 0.5 mcg/kg should be administered due to previously demonstrated inadequate
levels of sedation.9 (UWHealth Strong Recommendation, Moderate Quality of Evidence)
3. Preferred product: dexmedetomidine HCl 100 mcg/mL intranasal solution
4. Pharmacokinetics
4.1. Bioavailability: 65% (range: 35-93%) 4
4.2. Onset: 30-45 minutes (range: 20-68 minutes) 2,4,7-10
4.3. Peak effect: 90-105 minutes in adult patients (data on pediatric patients not available) 10
4.4. Duration of action: Dose dependent in pediatric patients - 1 mcg/kg dose 45 minutes (range: 40-100
minutes) 1,7,8 and 2 mcg/kg dose 95 minutes (range: 45-135 minutes) 7 ; adult patients receiving 1-1.5 mcg/kg
doses have previously demonstrated easily arousable sedation 180 minutes after administration. 10
5. IN adverse effects: Previous studies have not demonstrated adverse effects specific to the IN route of
administration.1-10

Fentanyl
1. Appropriate indications: Acute analgesia
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2. Dosing
2.1. Adult: 0.9-2.2 mcg/kg (maximum of 100 mcg/2 mL) initial dose; may repeat with 60 mcg doses every 5
minutes.19,120,121 (UWHealth Strong Recommendation, Moderate Quality of Evidence)
2.1.1. Use cautiously in patients 70 years of age and older due to lack of data. (UWHealth Strong
Recommendation, Low Quality of Evidence)
2.2. Pediatric (patients ≥10 kg and ≥1 year of age): 1-1.5 mcg/kg/dose. 11-17,122 ( UWHealth Strong
Recommendation, Moderate Quality of Evidence)
3. Preferred product: fentanyl citrate 50 mcg/mL intranasal solution
4. Pharmacokinetics
4.1. Bioavailability: 55- 77% 18
4.2. Onset: 5 to 10 minutes 15,16,18
4.3. Peak effect: about 20 minutes18
4.4. Duration of action: about 50 minutes 18
5. IN adverse effects: Inform patients that IN fentanyl may cause self-resolving unpalatable taste, watery eyes, nasal
congestion, or throat irritation in adult patients. Information regarding pediatric adverse effects with IN fentanyl is
not available. 15,19

Flumazenil
1. Appropriate indications: May be considered as initial route of administration for cases of suspected or actual
benzodiazepine overdose when the intravenous route is not available. 20,21 (UWHealth Weak/Conditional
Recommendation, Very Low Quality of Evidence)
2. Dosing
2.1. Adult: Not recommended for administration as has not been studied in this patient population. (UWHealth
Strong Recommendation, Low Quality of Evidence)
2.2. Pediatric: 40 mcg/kg with a maximum dose of 200 mcg (100 mcg in each nostril). 20,21 (UWHealth
Weak/Conditional Recommendation, Very Low Quality of Evidence)
3. Preferred product: flumazenil 100 mcg/mL intranasal solution
4. Pharmacokinetics
4.1. Bioavailability: Undetermined 21
4.2. Onset: <2 minutes 21
4.3. Peak effect: 2 minutes 21
4.4. Duration of action: Undetermined 21
5. IN adverse effects: N o IN route-specific adverse effects have been identified. 20,21

Glucagon
1. Not recommended for administration via the IN route, as has been previously demonstrated to have low
absorption. 28 Previous studies have used absorption enhancers to increase the bioavailability of IN administration,
and these are not available at UWHealth. 22-33 (UWHealth Strong Recommendation, Moderate Quality of Evidence)

Haloperidol
1. Haloperidol: Not recommended for administration via the IN route. Previous studies have not been able to
determine the optimal dose and the effect of repeat dosing using the IN route.123, 124

Hydromorphone
1. Appropriate indications: Acute analgesia
2. Dosing
2.1. Adult: 1-2 mg IN per dose is preferred.34-36 (UWHealth Strong Recommendation, Moderate Quality of
Evidence)
2.1.1. Redosing sooner than 20 minutes after the initial dose is not recommended.34-36 (UWHealth Strong
Recommendation, Moderate Quality of Evidence)
2.2. Pediatric: Not recommended, as has not been prospectively studied in this patient population. 34-36 (UWHealth
Strong Recommendation, Low Quality of Evidence)
3. Preferred product: hydromorphone HCl 1 mg/mL intranasal solution
4. Pharmacokinetics
4.1. Bioavailability: about 55% (1 mg dose range 26-71%; 2 mg dose range 36-78%) 36
4.2. Onset: 10-20 minutes 34,35
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4.3. Peak effect: 20-50 minutes 34,35
4.4. Duration of action: 180 minutes 35
5. IN adverse effects: Inform patients that IN hydromorphone may cause self-resolving unpalatable taste, nasal
itching, nasal congestion, or nasal stinging for a short period of time after administration.34,35

Ketamine
1. Appropriate indications: Procedural sedation and premedication for reducing preoperative anxiety. 37 -49,125
(UWHealth Strong Recommendation, Moderate Quality of Evidence)
2. Dosing
2.1. Adult: Use is not recommended due to a lack of data evaluating the use of IN ketamine in this population and
the suspected inability that therapeutic levels could be attained due to IN volume administration limits.37-49
(UWHealth Weak/Conditional Recommendation, Very Low Quality of Evidence)
2.2. Pediatric (patients ≥5 kg and ≥6 months of age)
2.2.1. Procedural sedation: 6-9 mg/kg 4 to 8 minutes prior to commencing for procedures anticipated to last
fewer than 30 to 40 minutes. 37,38,48 (UWHealth Strong Recommendation, Moderate Quality of
Evidence)
2.2.2. Premedication: 0.5-10 mg/kg between 15 to 30 minutes prior to procedure. Doses of at least 3 mg/kg
are preferred due to more available data. 40- 44,49,50 (UWHealth Strong Recommendation, Moderate
Quality of Evidence)
3. Preferred product: ketamine HCl 100 mg/mL intranasal solution
4. Pharmacokinetics
4.1. Bioavailability: 50% 44
4.2. Onset: about 5 minutes (range: 4-10 minutes) 37,38, 48
4.3. Peak effect: Not established 37-39 ,48,49
4.4. Duration of action: 40 minutes (range: 22-69 minutes) 37 -39,48,49
5. IN adverse effects: No IN route-specific adverse effects have been identified. 37-49

Lidocaine
1. Appropriate indications: Treatment of moderate to severe migraines when alternatives are ineffective and for
idiopathic second-division trigeminal neuralgia.51-55 (UWHealth Weak/Conditional Recommendation, Low Quality of
Evidence)
2. Dosing
2.1. Moderate to severe migraines
2.1.1. Adult: 20 mg in nostril of affected side if unilateral; 20 mg in each nostril if bilateral. 51-54 If moderate to
severe pain persists after 2 to 15 minutes, may repeat initial lidocaine dose.51,53 (UWHealth
Weak/Conditional Recommendation, Low Quality of Evidence)
2.1.2. Pediatric: Not recommended, as has not been studied in this patient population. (UWHealth Strong
Recommendation, Low Quality of Evidence)51-54
2.2. Idiopathic second-division trigeminal neuralgia
2.2.1. Adult: 8 mg in each nostril for a 16 mg total dose. 55 (UWHealth Weak/Conditional Recommendation,
Low Quality of Evidence)
2.2.2. Pediatric: Not recommended, as has not been studied in this patient population. 55 (UWHealth Strong
Recommendation, Low Quality of Evidence)
3. Preferred product: lidocaine HCl 40 mg/mL ( 4% ) intranasal solution
4. Pharmacokinetics
4.1. Bioavailability: 26% (range: 5-48%) 56
4.2. Onse t: 5-15 minutes51
4.3. Peak effect: Undetermined
4.4. Duration of action: Undetermined
5. IN adverse effects: Inform patients or caregivers about the potential for self-limiting local irritation (burning,
stinging, numbness), bitter taste, numbness of the throat, and nausea. 51

Lorazepam
1. Appropriate indications: Control of acute seizures. 57-60
2. Dosing
2.1. Adult: 0.1 mg/kg 59,60 (UWHealth Strong Recommendation, Moderate Quality of Evidence)
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13

2.2. Pediatric (patients ≥2 months of age): 0.1 mg/kg with consideration to a maximum dose of 4 mg.57,58
(UWHealth Strong Recommendation, Moderate Quality of Evidence)
3. Preferred product: lorazepam 4 mg/mL injection solution
4. Pharmacokinetics
4.1. Bioavailability: about 78% 59
4.2. Onset: about 5 minutes (range:1-25 minutes) 57,58
4.3. Peak effect: 30-105 minutes 59,60
4.4. Duration of action: about 60 minutes 58
5. IN adverse effects: Clinicians should inform patients or caregivers about the potential for poor taste, cool feeling in
nose and throat, and burning nasal sensation which is self-limiting in nature. 59,60

Midazolam
1. Appropriate indications: Procedural sedation prior to minor procedures or imaging and pre-induction for general
anesthesia and alternative therapy for pediatric seizures when the IV route is not available. 61,62
2. Dosing
2.1. Adult: Not routinely recommended due to the inability to administer therapeutic doses secondary to nasal
administration volume limitations, but may consider 0.2-0.3 mg/kg dose for patients (maximum of 10 mg due
to volume administration limitations) with prolonged seizures if other routes of administration are
unavailable. 63 (UWHealth Strong Recommendation, Very Low Quality of Evidence)
2.2. Pediatric
2.2.1. Procedural sedation and pre-induction for general anesthesia (patients ≥9 kg and ≥6 months of age):
0.2-0.5 mg/kg with consideration to a maximum dose of 10 mg due to volume administration
limitations.50,61,62 ,64-82 (UWHealth Strong Recommendation, Moderate Quality of Evidence)
2.2.2. Seizures (patients ≥1 month of age ): 0.2-0.5 mg/kg 63,83 -89 ( UWHealth Strong Recommendation,
Moderate Quality of Evidence). . Reference Status Epilepticus - Pediatric - Emergency
Department/Inpatient Clinical Practice Guideline for additional information.
3. Preferred product: midazolam HCl 5 mg/mL intranasal solution
4. Pharmacokinetics
4.1. Bioavailability: 50- 83% 64
4.2. Onset: Average 3-15 minutes (range: 0.5-19 minutes) 64 ,67,68,73 ,83, 86,88
4.3. Peak effect: about 25 minutes (10-48 minutes) 90,91
4.4. Duration of action: 21 to 60 minutes (dose-dependent) 61,64,67,73 ,79 ,92
5. IN adverse effects: Clinicians should inform patients or caregivers about the potential for self-resolving discomfort,
irritation, or burning sensation in the nasal passages after administration. 63 ,126

Morphine
1. Not recommended for administration via the IN route. Previous studies have used a mucoadherant to increase
bioavailability of IN administration which is not available at UWHealth. 93-97 (UWHealth Strong Recommendation,
Moderate Quality of Evidence)

Naloxone
1. Appropriate indications: May be considered as initial route of administration for cases of suspected or actual opioid
overdose when the intravenous route is not available.
2. Dosing
2.1. Adult: 2 mg administered as 1 mg/1 mL in each nostril. 98-104 (UWHealth Strong Recommendation, High
Quality of Evidence)
2.2. Pediatric: 0.2 mg in each nostril based upon limited data from a case report involving sedation reversal of a
benzodiazepine and opioid. 20 (UWHealth Strong Recommendation, Very Low Quality of Evidence)
2.3. The use of alternative routes of administration such as intravenous, intramuscular, and intraosseous should
be considered if an adequate response is not achieved within 8 to 10 minutes after the first IN dose. This is
due to the increased likelihood of orogastric absorption and reduced efficacy with subsequent IN
administrations, as the oral bioavailability of naloxone is low and the nasal mucosa likely would not be dry and
conducive for adequate absorption.
2.3.1. Consider doses up to 2 mg of naloxone via the intravenous route for cases of non-response to IN
naloxone in both pediatric patients and adults 99 (UWHealth Strong Recommendation, Low Quality of
Evidence)
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14

3. Product to be used: naloxone 1 mg/mL intranasal solution
4. Pharmacokinetics
4.1. Bioavailability: 4% 105
4.2. Onset: Undetermined 105
4.3. Peak effect: 6-9 minutes 105
4.4. Duration of action: Undetermined 105
5. IN adverse effects: No IN route-specific adverse events have been identified. 98-108

UW Health Implementation
Potential Benefits
ξ Increased patient comfort, decreased administration pain compared to IV placement or IM administration, and
faster administration time in situations where IV line access is challenging
ξ Increased workplace safety by potentially reducing healthcare employee needle sticks
ξ Decreased resources (e.g. nursing time for IV placement)

Potential Harms
ξ Staff unfamiliarity with intranasal administration compared to other routes
ξ Dosage miscalculations or inappropriate use of other route of administration dosing for intranasal route

Pertinent UWHealth Policies and Procedures
ξ UWHC Clinical Policy 8.76: Pain Management
ξ UWHC Clinical Policy 8.38: Adult Sedation Policy
ξ UWHC Clinical Policy 8.56: Pediatric Sedation Policy
ξ UWHC Sedation Nursing Practice Guideline
ξ Pain Care Fast Facts: Intranasal Analgesia Prior to Insertion of Nasogastric Tube – Pediatric
ξ Pain Care Fast Facts: Intranasal Analgesia Prior to Insertion of Nasogastric Tube – Adult

Patient Resources
None

Guideline Metrics
1. Utilization rate of intranasal medications in guideline
2. Adverse event rate of intranasal medications in guideline

Implementation Plan/Clinical Tools
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
will be reviewed for consistency and modified as appropriate.

ERX
ξ Dexmedetomidine HCl 100 mcg/mL intranasal solution [785204]
ξ Fentanyl citrate 50 mcg/mL intranasal solution [785209]
ξ Flumazenil 100 mcg/mL intranasal solution [785205]
ξ Hydromorphone HCl 1 mg/mL intranasal solution [785206]
ξ Ketamine HCl 100 mg/mL intranasal solution [785203]
ξ Lidocaine HCl 40 mg/mL (4%) intranasal solution [785202]
ξ Midazolam HCl 5 mg/mL intranasal solution [785196]
ξ Naloxone 1 mg/mL intranasal solution [785210]

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 clin ician’s judgment or
Copyright © 2017 University of Wisconsin Hospitals and Clinics Authority
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15

to establish a protocol for all patients. It is understood that some patients will not fit the clinical condition contemplate d
by a guideline and that a guideline will rarely establish the only appropriate approach to a problem.


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16

Appendix A. Evidence Grading Scheme
Figure 1. GRADE Methodology adapted by UWHealth 109




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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17

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Contact: Lee Vermeulen, CCKM@uwhealth.org Last Revised: 02/2017CCKM@uwhealth.org