Transcript Intranasal Medications

A Brief Introduction to
Intranasal Medications
Joseph Lewis, M.D.
Medical Director,
Honolulu EMS 2009
Intranasal Medications in the
Prehospital Setting
WHY?
The problem!
• The CDC estimates:
o600,000 percutaneous
injuries each year involving
contaminated sharps.
High Risk Patients in the field!
HIV+ patients = 4.1 to 8.3/100 transports
Marcus et al, Ann Em Med, 1995
*Hepatitis >10 patients /100
patients
• High risk environments
o Altered patients, combative
o Scene control issues
o Moving ambulance
Intranasal Medication
Administration
• Intranasal Medication
administration offers a truly
“Needleless” solution to drug
delivery.
Intranasal Medication
Administration: Basic Concepts
Its easy and convenient because…
• Almost everyone has a nose
• No special training is required to deliver the
medication
• No shots are needed
• It is painless
• It eliminates any risk of a needle stick to
you, the medical provider
Intranasal Medication Administration:
Factors Affecting Drug Absorption
• Volume and concentration:
• Best: Low volume & High concentration.
• Too large a volume or too weak a
concentration may lead to failure because
the drug cannot be absorbed in high
enough quantity to be effective.
• Volumes over 1 ml per nostril are likely too
dilute and may result in runoff out of the
nostril.
Intranasal Medication Administration:
Factors Affecting Drug Absorption
• Delivery system characteristics:
o Atomization results in higher
bioavailability than either spray or
drops.
o For this reason, nasal drugs must
use an atomized drug delivery
system.
Intranasal Medication Administration:
Factors Affecting Drug Absorption
• Nasal mucosal characteristics:
If there is something wrong with the nasal
mucosa it may not absorb medications
effectively.
o Examples:
o
 Vasoconstrictors like cocaine prevent
absorption.
 Bloody nose, nasal congestion, mucous
discharge all can prevent mucosal contact of
drug.
 Destruction of nasal mucosa from surgery or
cocaine abuse – no mucosa to absorb the drug.
Mucosal Atomization Device (MAD)
• MAD - Mucosal
Atomization device:
Device designed to
allow emergency
personnel to delivery
nasal medications as
an atomized spray.
o Broad 30-micron
spray ensure
excellent mucosal
coverage.
o
Nasal Drug Delivery: What
Medications?
• FDA approved:
o
A large number of medications ranging from
nasal steroids to antibiotics to opiate
anesthetics are FDA approved.
• Non-FDA approved:
o
Many other medications are effective via the
nasal mucosa, but the pharmaceutical
companies have not pursued FDA clearance
for nasal delivery for a number of financial
reasons as opposed to medical reasons.
Nasal Drug Delivery in EMS:
What Medications?
• Drugs of interest to EMS systems:
o
o
o
o
Intranasal naloxone (Narcan)
Intranasal midazolam (Versed)
Nitroglycerine
Others
Intranasal (IN) Naloxone
• Background
o
Absorption of IN naloxone almost as fast
as IV in both animal and human models
 Hussain et al, Int J Pharm, 1984
 Loimer et al, Int J Addict, 1994
 Loimer et al, J Psychiatr Res, 1992
o
“Atomization” of medications show much
better absorption via the IN route then IV
 Thorsson et al, Br J Clin Pharmacol, 1999
The Denver Experience…
• Denver Health Paramedic System
Administering 600-800 doses of
naloxone (Narcan®) a year intravenously
to patients
o Sheathed needles were not used
properly
o No change in incidence of bloodborne
exposures
o
Prehospital IN Naloxone
• Mucosal Atomizer Device (MAD)
o Single-use
o Disposable
o Fits on standard syringe
Mucosal Atomizer Device (MAD)
The white plastic you
see on this standard 2cc
luer lock syringe is the
atomizer and it costs
about 23 cents.
IN Naloxone by Paramedics
IN Naloxone by Paramedics
Prehospital IN Naloxone
• Results (cont.).
o
43/52 (83%) = “IN Naloxone Responders.”
 Mean time = 3.9 minutes (range 1-11 min.).
 Median time = 3 min.
 Mean time from first contact = 9.9 min.
 Median time from first contact = 8 min.
o
9/52 (17%) = “IN Non-responders.”
 4 patients noted to have “epistaxis,” “trauma,”
or “septal abnormality.”
Prehospital IN Naloxone
• Results (cont.)
o IN Naloxone Responders
 12/43 (29%) got no IV in the field
 7/43 (16%) required additional dose of IV naloxone
 “leakage from L nares”
 “aroused slowly”
 “recurrent somulence”
 “2mg IV given due to slow response”
 “lower IN dose - spilled filling syringe”
 “pt responded within 90-120 sec, but still had
decr LOC
Prehospital IN Naloxone
• Take away lessons for nasal naloxone:
Dose and volume – higher concentration preferred so
use 1mg/ml IV solution.
Delivery – immediately on decision to treat inject
naloxone into nose with MAD, then begin standard
care.
Successful awakening eliminates the need for any IV
or further ALS care.
Awakening is gradual, but adequate respiratory efforts
occur as fast or faster than IV naloxone due to no
delays with IV start.
Not 100% effective so failures with IN naloxone need
to be followed with IV naloxone.
Prehospital IN Midazolam
• Why intranasal midazolam for seizures in
the EMS setting?
No needles, no need for an IV in a seizing
patient.
o Rapid delivery – No delays in IV attempts.
o Socially acceptable: No need for rectal drug
administration.
o
IN Midazolam
• Supporting data:
o Nasal
midazolam has been extensively
studied for over a decade with hundreds
of studies published regarding its
effectiveness for sedating children.
o Very effective for treating acute seizures
and status epilepsy.
IN Midazolam
• Seizures.
o
Lahat et al, BMJ, 2000.
 Prospective study: IN midazolam versus IV
diazepam for prolonged seizures (>10 minutes)
in children.
 Similar efficacy in stopping seizures (app.
90%).
 Time to seizure cessation:
 IV Valium: 8.0 minutes.
 IN Versed: 6.1 minutes.
IN Midazolam
• Lahat et al, BMJ, 2000 (cont):
o
Conclusions:
 IV diazepam and IN midazolam have similar
efficacy at controlling prolonged seizures in
children.
 IN midazolam controls seizures more rapidly
because there is no delay in establishing an IV.
IN Midazolam
• Sheepers et al, Seizure, 2000.
IN midazolam for treatment of severe epilepsy
in adults.
 Results: IN midazolam effective in 94% of seizures.
 Conclusion: IN midazolam an effective method for
controlling seizures and is a “more acceptable and
dignified route” than rectal diazepam.
IN Midazolam
Take away lessons for nasal
midazolam:
• Dose and volume: Higher concentration
required - use 5mg/ml IV solution.
• Dosing calculations are difficult: Use a
predefined age or weight based table to
determine dose.
• Give max of 1 ml per nostril and 10 mg total.
• Deliver immediately on decision to treat:
Atomize into nose with MAD, then begin
standard care.
• Efficacy: Not quite 100% effective so failures
with nasal may need follow-up with IV therapy.
Dosage Charts
Midazolam 5mg/ml concentration
Dosing chart
Total kg wt X 0.2 mg = total mg dose of Midazolam (maximum of 10 ml
Patient age
(years) Weight (kg)
IN Midazolam
volume
Volume
Dose (mg)
Neonate 3 kg
0.3 ml
0.6 mg
<1 yr 6 kg 0.4 ml
1.2 mg
1 yr 10 kg 0.5ml
2.0 mg
2 yr 14 kg 0.7 ml
2.8 mg
3 yr 16 kg 0.8 ml
3.2 mg
4 yr 18 kg 0.9 ml
3.6 mg
5 yr 20 kg 1.0 ml
4.0 mg
6 yr 22 kg 1.0 ml
4.4 mg
7 yr 24 kg 1.1 ml
4.8 mg
8 yr 26 kg 1.2 ml
5.2 mg
9 yr 28 kg 1.3 ml
5.6 mg
10 yr 30 kg 1.4 ml
6.0 mg
11 yr 32 kg 1.4 ml
6.4 mg
12 yr 34 kg 1.5 ml
6.8 mg
Small teenager
40 kg 1.8 ml
8.0 mg
Adult or full-grown teenager
> 50 kg 2.0 ml
10.0 mg
in
ml*
Example Standing orders IN
Medications Hawaii State EMS
•
•
•
•
•
•
Midazolam intranasal IN for seizure
Dose 0.2 mg/kg IN up to maximum of 10 mg
Drug comes 5mg/ml
Patient weights 20 kg
Calculated Dose 4 mg versed
Give 0.8 ml via atomizer in one nare, which is
under the maximum of 1 ml per nare.
Example Standing orders IN
Medications Hawaii State EMS
•
•
•
•
•
•
Midazolam intranasal IN for seizure
Dose 0.2 mg/kg IN
Drug comes 5mg/ml
Patient weights 40 kg
Calculated Dose 8 mg versed
Give 1.6 ml via atomizer, 0.8 ml in each nare,
remembering that the desired upper limit is 1
ml per nostril.
Example Standing orders IN
Medications Hawaii State EMS
•
•
•
•
•
Midazolam intranasal IN for seizure
Dose 0.2 mg/kg IN
Drug comes 5mg/ml
Patient weights 80 kg
Calculated Dose 16 mg so give max dose of
10 mg only!
• Give 2 ml via atomizer, 1 ml in each nare.
Dosage Charts
Midazolam 5mg/ml
concentration
Dosing chart
Total kg wt X 0.2 mg = total mg dose of Midazolam (maximum of 10 ml
Patient age
(years) Weight (kg)
IN Midazolam
volume in
Volume
Dose (mg)
Neonate 3 kg
0.3 ml
0.6 mg
<1 yr 6 kg 0.4 ml
1.2 mg
1 yr 10 kg 0.5ml
2.0 mg
2 yr 14 kg 0.7 ml
2.8 mg
3 yr 16 kg 0.8 ml
3.2 mg
4 yr 18 kg 0.9 ml
3.6 mg
5 yr 20 kg 1.0 ml
4.0 mg
6 yr 22 kg 1.0 ml
4.4 mg
7 yr 24 kg 1.1 ml
4.8 mg
8 yr 26 kg 1.2 ml
5.2 mg
9 yr 28 kg 1.3 ml
5.6 mg
10 yr 30 kg 1.4 ml
6.0 mg
11 yr 32 kg 1.4 ml
6.4 mg
12 yr 34 kg 1.5 ml
6.8 mg
Small teenager
40 kg 1.8 ml
8.0 mg
Adult or full-grown teenager
> 50 kg 2.0 ml
10.0 mg
ml*