Feature

The Intranasal Route as an

Alternative Method of
Medication Administration
Calvin Tucker, PharmD, BCPS, BCCCP
Lyn Tucker, PharmD
Kyle Brown, PharmD

Intranasal drug administration is a less invasive method of drug delivery that is easily accessible for adult
and pediatric patients. Medications administered by the intranasal route have efficacy comparable to
intravenous administration and typically have superior efficacy to subcutaneous or intramuscular routes.
The intranasal route is beneficial in emergent situations when the intravenous route is not available. The
intranasal route is safe and effective in various indications, and therapeutic systemic concentrations of
medication can be attained via this route. As the evidence for and comfort with intranasal administration
continue to grow, guidance on correct technique, medications, and dosing is vital for appropriate use.
This article reviews the process and practices of appropriate intranasal medication administration. (Critical
Care Nurse. 2018;38[5]:26-32)

he nasal cavity comprises an extensive plexus of capillary beds with monolayer ciliated epithe-

T lium that facilitates achieving effective blood levels of topically administered medications while
avoiding the intravenous route of administration.1,2 Similar to the intravenous route, the intra-
nasal route avoids first-pass metabolism, allowing medications to enter systemic circulation without being
altered by the hepatic metabolic processes. The avoidance of gastrointestinal and hepatic metabolism
allows more drug to be rapidly and predictably bioavailable.1,2
If intravenous access cannot be established quickly or requires multiple attempts, precious time can
be lost before sufficient treatment is provided to the patient. Using the intranasal route can offer superior

CE 1.0 hour, Pharma 0.25, CERP A

This article has been designated for CE contact hour(s). The evaluation tests your knowledge of the following objectives:
1. Explain the indications and advantages of intranasal medication administration
2. Describe appropriate techniques for successful intranasal medication administration
3. Identify dosing considerations for the administration of midazolam, fentanyl, naloxone, and ketamine via the intranasal route
To complete evaluation for CE contact hour(s) for activity C1853, visit www.ccnonline.org and click the “CE Articles” button. No fee for AACN members. This
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efficacy and be more reliable than subcutaneous and
Intranasal Administration
intramuscular routes of administration.3 It is imperative
that nurses are familiar with routes of administration, • Using a 1-mL or 3-mL syringe and needle,
such as intranasal, that can be used emergently to draw up the total amount of medication to be
quickly deliver medication to patients. The intranasal administered. Alternatively, a prefilled syringe
route is safe, convenient, and effective for medication
formulation may be provided.
administration and avoids the disadvantages of other
• In addition to the dose to be delivered, draw
alternative routes of administration.3
up an extra 0.1 mL of medication into the
Not all medications are produced in an intranasal
formulation; therefore, parenteral formulations are syringe to account for dead space. This action
commonly used for intranasal administration.4 Droplet is not required when a prefilled syringe is used.
application and atomization are the 2 main modes of • Remove the needle and attach the atomizer to
intranasal administration. The droplet method requires the syringe.
the medication to be delivered 1 drop at a time; however, • Suction nostrils to remove excess mucous,
if the medication is delivered too fast, it will accumulate which can aid administration and absorption.
at the back of the patient’s throat and will not be absorbed • Using a free hand to hold the head stable,
into the systemic circulation.1,5 Appropriate positioning place the tip of the device gently but firmly
of the patient’s head and the patient’s ability to lie motion- against the nostril aiming slightly up and out-
less are imperative to administer medications by the ward (toward the top of the ipsilateral ear).
droplet method. Because of the concerns of absorption The head does not need to be tilted back.
and patient positioning, however, the droplet method
• Rapidly compress the syringe plunger to
has minimal use in acute care facilities; therefore, we
deliver half of the medication into the nostril
focus on atomization delivery devices in this review.
(if the plunger is not pushed fast enough,
Atomizers administer medications as a fine mist of
particles, broadly distributing the medication across atomized misting of the medication will not
the nasal mucosa, thereby increasing medication bio- be achieved and swallowing of the medication
availability and reducing the amount of medication lost may occur).
in the back of the throat. The suggested volume for intra- • Repeat for the other nostril.
nasal administration can range from 0.1 mL to 0.3 mL,
with a maximum of 1 mL per nostril. As the volume of
medication increases, the concern of excessive drainage atomizer devices are commercially available. The devices
out of the nose to the back of the throat is increased.4 may differ in their amount of dead space, the need for
Atomizers may also have dead space of 0.1 mL or more a syringe, the patient positioning required, reusability of
and this should be accounted for by adding it to the final the device, and accuracy of the volume administered.
medication volume to avoid underdosing. Various For acute care facilities, atomizers preferably should be
single use, syringe compatible, able to be used from any
position, contain minimal dead space, and administer a
Authors
consistent, accurate volume.
Calvin Tucker is the Emergency Medicine/Critical Care Pharma-
cist at Baptist Health, Jacksonville, Florida. Appropriate administration techniques are critical to
successful use of atomization devices. Ensuring the nasal
Lyn Tucker is a clinical pharmacist, Pediatric Emergency Department,
Wolfson Children’s Hospital, Jacksonville, Florida. passages and facial region do not have any injuries and
Kyle Brown is a critical care specialist at Memorial West, Pem- are clear of mucus, blood, and other debris is critical to
broke Pines, Florida. prevent the obstruction of medication absorption. Most
Corresponding author: Calvin Tucker, PharmD, BCPS, BCCCP, 800 Prudential Drive, atomizers will have a conical shape to form a seal with
Jacksonville, FL 32207 (email: calvin.tucker@jaxhealth.com). the nostril, preventing any expulsion of fluid. This coni-
To purchase electronic or print reprints, contact the American Association of Critical- cal shape allows patients to be placed in any position
Care Nurses, 101 Columbia, Aliso Viejo, CA 92656. Phone, (800) 899-1712 or
(949) 362-2050 (ext 532); fax, (949) 362-2049; email, reprints@aacn.org. when medications are administered through an atomizer.

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 In contrast, the droplet method requires the patient’s to achieve the desired response. The intranasal dose will
head to be tilted backward before medication adminis- likely be significantly higher compared with the intrave-
tration. In most instances, the medication will be con- nous dose, due to the bioavailability of the nasal mucosa.
tained in a syringe (3 mL or 5 mL) and the atomizer Typically, effects will be seen within 3 to 5 minutes of
will be attached. Aim upward and slightly outward administration and peak within 10 to 15 minutes, although
toward the top of the ear to target turbinates and olfac- there could be some variation depending on the specific
tory mucosa to maximize rapid absorption. Briskly com- characteristics of the medication.
press the syringe plunger to provide a mist of medication Several medications have been evaluated for intrana-
that will cover the nasal mucosa. sal administration, including fentanyl, sufentanil, hydro-
Compared with droplets, mists deposit on noncili- morphone, ketamine, midazolam, dexmedetomidine,
ated surfaces and have a slower clearance. The size of haloperidol, calcitonin, sumatriptan, naloxone, flumaze-
medication particles also affects nasal distribution; nil, and glucagon. However, the majority of supporting
particles between 10 and 20 μm deposit on the nasal evidence and experience in clinical practice deal with use
mucosa and then are absorbed in the blood. If blood of a select group of medications, namely, midazolam,
flow to the nasal mucosa is poor, drug absorption will be naloxone, fentanyl, and ketamine. Therefore, our review
adversely affected. To improve absorption and effec- focuses on this group.
tiveness, it is recommended that one-half the dose be
applied to each nostril to cover more surface area. Allow Midazolam
a minimum of 5 to 10 minutes before administering Midazolam can be given intravenously, intramuscu-
subsequent doses. The intranasal route is generally larly, buccally, and rectally, as well as via the nasal mucosa.
well tolerated; the most commonly reported adverse It is lipid soluble at physiologic pH levels, which allows
effects are nasal burning, irritation, and bitter taste, it to have a rapid onset of action.2 Midazolam is safe and
but these may vary depending on the physical proper- effective when given via the intranasal route to patients
ties of the medication. undergoing various diagnostic studies and minor surgi-
cal procedures, such as computerized tomography,
Medications echocardiography, dental procedures, and suture lacera-
Intranasal medication administration can be benefi- tion. The incidence of adverse effects is low; the most
cial for a variety of indications, including management common adverse effect reported after the administration
of pain, anxiety, and hypoglycemia; opiate reversal; and of intranasal midazolam is a burning sensation or irrita-
seizure control. However, a limited number of medica- tion in the nose lasting for 30 to 45 seconds and a bitter
tions are formulated for intranasal administration and taste in the mouth.2 Intranasal administration of the intra-
the product made for injection is commonly used for venous formulation has been reported in the literature,
intranasal using a needleless syringe either by dripping the solution
Intranasal delivery can be beneficial for delivery. into the nose or using a mucosal atomization device.6
management of pain, anxiety, and hypo- Parenteral There are various recommendations regarding
glycemia, as well as opiate reversal and formula- intranasal dosing of midazolam for adults and chil-
seizure control. tions are dren. The actual dose administered depends on the
not cre- volume that can be administered per nostril and the
ated for nasal delivery; therefore, the drug formulation, concentration of the medication. Doses between 2.5 mg
concentration, and/or dosing volume may not be opti- and 7.5 mg are effective.6 When studied, each dose was
mal for intranasal delivery. Typically, the most concen- given using a concentrated midazolam product in only
trated parenteral formulations are used, so the smallest 1 nostril; therefore, higher doses possibly can be used.
volume is administered.6 Lipid solubility and being In children, doses of 0.2 to 0.4 mg/kg (maximum, 10
small enough to permeate the nasal mucosa are also mg) divided between each nostril were commonly used
essential qualities for medications to be administered (see Table).6,7 Administration of 0.5 mL was associated
successfully via the intranasal route.1,2 A common prob- with a statistically shorter time to onset of minimal
lem with intranasal delivery is that the dose is inadequate sedation compared with a volume of administration

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 Table Medication concentrations and doses for intranasal administration
Parenteral Intranasal Intranasal
Medication Indication concentration concentration formulation Dose
Midazolam Sedation 5 mg/mL NA No Sedation: 0.4 mg/kg
Seizures Seizures: 0.2-0.3 mg/kg
Maximum: 10 mg
Naloxone Opiate overdose 1 mg/mL PFS 4 mg/0.1 mL Yes 0.01 mg/kg
Maximum: 2 mg
Fentanyl Pain 50 +g/mL 80 +g/mL Yes 1.5-2 +g/kg
Maximum: 100 +g
Ketamine Pain 100 mg/mL NA No Pain: 0.5-1 mg/kg
Sedation Pediatric sedation: 3-6 mg/kg
Adult sedation: 6-10 mg/kg
Maximum: 200 mg
Lidocaine Pretreatment 2% NA No Pretreatment: 0.2 mL in each nostril about
Nasal procedures 4% 3-5 min before midazolam administration
Nasal procedures: 0.75 mL in each nostril.
Wait 3 min for full anesthetic effect
before procedure; may repeat half the
dose, if necessary.
Abbreviations: NA, not applicable; PFS, prefilled syringe.

of 1 mL; however, studies support the recommendation experience in using naloxone injection via the nasal route
that it is acceptable to administer up to 1 mL per nostril. when treating known or suspected opioid overdose. Nal-
Depending on the indication, higher or repeated doses oxone hydrochloride injection is available as a 1 mg/mL
may be required as body weight increases or for certain solution and the intranasal formulation is available at a
indications such as seizures. The administration of mid- concentration of 4 mg/0.1 mL. For reversal of respiratory
azolam intranasally can burn; therefore, 4 mg of lidocaine depression due to overdoses involving therapeutic amounts
(4% for adults and 2% for children) can be adminis- of prescription opioids, smaller naloxone doses of 0.04
tered before giving midazolam.7 mg to 0.4 mg can be given; however, the only intranasal
dose proven to be effective is 2 mg.8,10 Naloxone has been
Naloxone given successfully via the intranasal route, with either
Naloxone is a pure opioid antagonist with no ago- the 1 mg/mL parenteral formulation or the 4 mg/0.1 mL
nist activity. Although naloxone’s mechanism of action nasal formulation.
is not fully understood, it appears the drug works by
competing with other opioids for the μ-opioid, g-opioid, Fentanyl
and b-opioid receptor sites in the central nervous sys- Fentanyl preparations have been introduced as an alter-
tem, with the greatest affinity for the μ-opioid recep- native approach to immediate-release morphine for the
tor.8 Naloxone is a quick-acting drug; the distribution treatment of pain and in a variety of administration forms.
of naloxone after intravenous administration is rapid, In pharmacokinetic studies of nasal administration of opi-
and the response to naloxone can often be described oids, rapid uptake and action have been shown. There is a
as dramatic and lifesaving. Naloxone is also rapidly formulation specifically for intranasal administration avail-
absorbed from the nasal cavity and was as effective as able in 50 μg, 100 μg, and 200 μg doses.11 A median time to
intravenous administration at reversing the effects of reach peak serum concentration value between 12 and 15
an opioid overdose.9 minutes and a bioavailability of 89% for the intranasal fen-
Pharmacokinetic data for intranasal administration tanyl formulation have been reported.11 The intranasal fen-
continue to become more robust. When administered tanyl formulation may not be readily available; therefore,
intranasally, the onset is fairly rapid and lasts up to 90 the intravenous 50 μg/mL product is most commonly
minutes.9 Emergency medical personnel have extensive used for intranasal administration.

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 The efficacy of intranasal fentanyl has been reported hours. When given intranasally, ketamine can be dosed
in several studies in which rapid time to analgesic effect at 0.5 mg/kg to 0.75 mg/kg.15
and superior pain intensity difference at 10 minutes There is no intranasal formulation for ketamine;
have been shown. Intranasal fentanyl is as effective an therefore, the injection product is commonly used at a
analgesic as intramuscular morphine in children treated concentration of 100 mg/mL. Intranasal ketamine has
in the emergency department.12 Comparable benefits comparable efficacy to intravenous and intramuscular
were also found between intranasal fentanyl and intra- morphine in adult patients.14 Intranasal ketamine can
venous morphine in the attenuation of pain associated reduce pain scores to a clinically significant degree in
with long-bone fractures in children treated in the approximately 88% of patients.15 Most data are from
emergency department.13 children; however, there is increasing evidence that
The data are somewhat limited, however, regarding intranasal ketamine can be effective in adult popula-
the use of intranasal fentanyl in adult patients in emer- tions, as well.
gency settings. For adult and pediatric patients with
moderate to severe pain due to acute musculoskeletal Conclusion
injuries, intranasal fentanyl at a dose of 1.5 μg/kg was The intranasal route is a viable alternative by which
effective when compared to tramadol alone in patients to administer medications, especially when more con-
with moderate to severe pain due to acute musculo- ventional routes are not available; it has been proven
skeletal injuries.12 safe and effective in various indications and capable of
Intranasal fentanyl is also approved for the manage- attaining therapeutic systemic concentrations. The intro-
ment of breakthrough pain in adult patients with cancer duction of atomization devices improved delivery directly
who are already receiving maintenance opioid therapy to the surface of the nasal mucosa and improved drug
for chronic cancer pain. In clinical studies of patients absorption. Most medications studied for intranasal
with cancer, intranasal fentanyl provided clinically rele- administration do not have an intranasal formulation;
vant reductions in pain intensity with superior efficacy therefore, the most concentrated parenteral formulation
and patient preference, compared with oral transmuco- is commonly used for the intranasal route. If the volume
sal fentanyl citrate.13 Because of the short duration of is too large or administered too rapidly, suboptimal
fentanyl, additional pain medications may be needed absorption and loss of drug into the pharynx can result,
shortly after intranasal administration to ensure ade- compromising the drug’s effectiveness. Additional stud-
quate pain control is maintained. ies of midazolam are needed to identify the volumes
appropriate for intranasal administration.
Ketamine The intranasal route has several advantages over
Ketamine, an N-methyl D-aspartate antagonist, has intravenous or intramuscular administration, including
been widely studied for its efficacy in analgesia and shorter time to administration, minimal training or
anesthesia. However, administration of ketamine via specialized skill for administration, and minimal patient
the intranasal route, especially in adults, has only discomfort. The monitoring parameters for intranasal
recently been studied and requires further elucidation administration are similar to when the medications are
in the acute setting. To our knowledge, the efficacy and given by other routes of administration; there are mini-
adverse-effect profile of intranasal ketamine have not mal adverse effects specific to the intranasal route.
yet been well compared with those of opiates in the Not all medications are suitable for delivery via the
emergency department and prehospital setting; between intranasal route. Only drugs that have high potency and
56% and 88% of patients experienced clinically signifi- are available in concentrated preparations are appropri-
cant pain relief, according to one study.14 When adminis- ate, because a volume greater than 1 mL per nostril may
tered intranasally, ketamine has a bioavailability of 45% not be reliably administered.
and blood levels correspond well with analgesic effect. The evidence supporting intranasal administration
Intranasal ketamine resulted in detectable blood levels is growing; several medications have been identified as
after 2 minutes, with a maximum concentration apparent suitable for intranasal delivery. The intranasal route is
at 30 minutes and reduced pain reported for at least 3 commonly used in children; however, use in adults,

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specifically for pain and narcotic reversal, is becoming 3. Djupesland PG. Nasal drug delivery devices: characteristics and perfor-
mance in a clinical perspective—a review. Drug Deliv Transl Res. 2013;
more prevalent. As use of intranasal drug delivery con- 3(1):42-62.
4. Tsze DS, Ieni M, Fenster DB, et al. Optimal volume of administration of
tinues to increase, formulations specific for intranasal intranasal midazolam in children: a randomized clinical trial. Ann Emerg
administration will need to be developed and additional Med. 2017;69(5):600-609.
5. Collopy KT, Snyder SR. Intranasal drug administration: an innovative
studies will be needed to validate the intranasal route as approach to traditional care. EMS World. 2011;40(5):45-50.
safe and effective. &&1 6. Bancke LL, Dworak HA, Rodvold KA, et al. Pharmacokinetics, pharma-
codynamics, and safety of USL261, a midazolam formulation optimized
for intranasal delivery, in a randomized study with healthy volunteers.
Financial Disclosures Epilepsia. 2015;56(11):1723-1731.
None reported. 7. Chiaretti A, Barone G, Rigante D, et al. Intranasal lidocaine and midaz-
olam for procedural sedation in children. Arch Dis Child. 2011;96(2):160-163.
8. Robinson A, Wermeling DP. Intranasal naloxone administration for treat-
ment of opioid overdose. Am J Health Syst Pharm. 2014;71(24):2129-2135.
Now that you’ve read the article, create or contribute to an online discussion about 9. Merlin MA, Saybolt M, Kapitanyan R. Intranasal naloxone delivery is an
this topic using eLetters. Just visit www.ccnonline.org and select the article you want alternative to intravenous naloxone for opioid overdoses. Am J Emerg Med.
to comment on. In the full-text or PDF view of the article, click “Responses” in the 2010;28(3):296-303.
middle column and then “Submit a response.” 10. Del Pizzo J, Callahan JM. Intranasal medications in pediatric emergency
medicine. Pediatr Emerg Care. 2014;30(7):496-504.
11. Thronæs M, Popper L, Eeg M, et al. Efficacy and tolerability of intranasal

See also
fentanyl spray in cancer patients with breakthrough pain. Clin Ther. 2015;
37(3):585-596.
To learn more about medication administration, read “Medication 12. Chew KS, Shaharudin AH. An open-label randomised controlled trial
Errors in Cardiopulmonary Arrest and Code-Related Situations” by on the efficacy of adding intranasal fentanyl to intravenous tramadol in
patients with moderate to severe pain following acute musculoskeletal
Flannery and Parli in the American Journal of Critical Care, January injuries. Singapore Med J. 2016;58(10):601-605.
2016;25:12-20. Available at www.ajcconline.org. 13. Mercadante S, Vellucci R, Cuomo A, et al. Long-term efficacy and tolera-
bility of intranasal fentanyl in the treatment of breakthrough cancer pain.
Support Care Cancer. 2015;23(5):1349-1354.
References 14. Shimonovich S, Gigi R, Shapira A, et al. Intranasal ketamine for acute
1. Corrigan M, Wilson SS, Hampton J. Safety and efficacy of intranasally traumatic pain in the Emergency Department: a prospective, random-
administered medications in the emergency department and prehospi- ized clinical trial of efficacy and safety. BMC Emerg Med. 2016;16(1):43.
tal settings. Am J Health Syst Pharm. 2015;72(18):1544-1554. 15. Andolfatto G, Willman E, Joo D. Intranasal ketamine for analgesia in the
2. Zelcer M, Goldman RD. Intranasal midazolam for seizure cessation in emergency department: a prospective observational series. Acad Emerg
the community setting. Can Fam Physician. 2016;62(7):559-561. Med. 2013;20(10):1050-1054.

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 CCN Fast Facts CriticalCareNurse
The journal for high acuity, progressive, and critical care nursing

The Intranasal Route as an Alternative

Method of Medication Administration

he intranasal route is a viable alternative by • The monitoring parameters for intranasal

T which to administer medications, especially

when more conventional routes are not avail-
able; it has been proven safe and effective in various
administration are similar to when the medica-
tions are given by other routes of administra-
tion; there are minimal adverse effects specific to
indications and capable of attaining therapeutic sys- the intranasal route.
temic concentrations. The introduction of atomiza-
tion devices improved delivery directly to the surface • Only drugs that have high potency and are avail-
of the nasal mucosa and improved drug absorption. able in concentrated preparations are appropri-
ate for delivery via the intranasal route, because
• Most medications studied for intranasal adminis- a volume greater than 1 mL per nostril may not
tration do not have an intranasal formulation; be reliably administered.
therefore, the most concentrated parenteral formu-
lation is commonly used for the intranasal route. • The evidence supporting intranasal administra-
tion is growing; several medications have been
• If the volume is too large or administered too identified as suitable for intranasal delivery. The
rapidly, suboptimal absorption and loss of drug intranasal route is commonly used in children;
into the pharynx can result, compromising the however, use in adults, specifically for pain and
drug’s effectiveness. narcotic reversal, is becoming more prevalent.

• Additional studies of midazolam are needed to • As use of intranasal drug delivery continues to
identify the volumes appropriate for intranasal increase, formulations specific for intranasal
administration. administration will need to be developed and
additional studies will be needed to validate the
• The intranasal route has several advantages over intranasal route as safe and effective. &&1
intravenous or intramuscular administration,
including shorter time to administration, minimal
training or specialized skill for administration, and
minimal patient discomfort.

Tucker C, Tucker L, Brown K. The intranasal route as an alternative method of medication administration. Critical Care Nurse. 2018;38(5):26-32.

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The Intranasal Route as an Alternative Method of Medication Administration
Calvin Tucker, Lyn Tucker and Kyle Brown
Crit Care Nurse 2018;38 26-31 10.4037/ccn2018836
©2018 American Association of Critical-Care Nurses
Published online http://ccn.aacnjournals.org/
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