2. PHARMACOLOGIC CATEGORY
Naloxone was developed in 1960 as a novel opioid antagonist with fewer side effects than its
predecessors.
in 1971 the American Food and Drug Administration (F.D.A.) authorized its use to treat overdoses
caused by opiates.
Antidote
Opioid Antagonist
3. INDICATIONS
Opioid overdose: For the complete or partial reversal of opioid depression induced by natural and
synthetic opioids ( propoxyphene, methadone, nalbuphine, butorphanol, pentazocine).
For the diagnosis of suspected or known acute opioid overdosage.
Reverse overdose effects of the two opioid agents, fentanyl and meperidine, used in the technique
of IV conscious sedation.
Off-Label: Opioid-induced pruritus.
4. Naloxone antagonizes the opioid effects by competing for the same
receptor sites in the mu-opioid receptors causing the rapid removal of any
other drugs bound to these .
Recently, naloxone has been shown to bind all three opioid receptors (mu,
kappa and gamma) but the strongest binding is to the mu receptor.
MECHANISM OF ACTION
5. PHARMACOKINETICS
• ONSET OF ACTION:
Endotracheal, IM, SubQ: 2 to 5 minutes.
Inhalation via nebulization: ~5 minutes or Intranasal: ~8 to 13 minutes.
IV: ~2 minutes
• DURATION:
30 to 120 minutes depending on route of administration.
IV has a shorter duration of action than IM administration.
• ABSORPTION:
Intranasal, IM, SubQ.
• PROTEIN BINDING:
It is relatively weak. albumin is the major binding constituent but significant binding of naloxone also occurs to
plasma constituents other than albumin.
6. METABOLISM: is hepatically metabolized and primarily undergoes glucuronidation to form
naloxone-3-glucuronide.
BIOAVAILABILITY: 43% to 54% (nasal compared to 0.4 mg IM dose)
TIME TO PEAK: IM, SubQ: 15 minutes; Intranasal: 19.8 to 30 minutes
HALF-LIFE ELIMINATION: Neonates: Mean 3.1 ± 0.5 hours; Adults: IM, IV, or SubQ: 0.5 to 1.5 hours;
Intranasal: ~2 hours
EXCRETION: Urine (25%- 40% is excreted as metabolites within 6 hours)
9. DOSING
OPIOID OVERDOSE:
IV, IM, SubQ: Initial: 0.4 to 2 mg; may need to repeat doses every 2 to 3 minutes.
A lower initial dose (0.1 to 0.2 mg) should be considered for patients with opioid dependence to
avoid acute withdrawal or if there are concerns regarding concurrent stimulant overdose.
After reversal, may need to readminister doses at a later interval ( 20 to 60 minutes) depending on
type/duration of opioid. If no response is observed after 10 mg total, consider other causes of
respiratory depression.
Endotracheally (off-label route) as 2 to 2.5 times the initial IV dose (0.8 to 5 mg).
10. OFF- LABEL
Continuous infusion (off-label dosing): Used in exposures to long-acting opioids, sustained release
product, and symptomatic body packers after initial naloxone response.
the calculate for dosage/hour is based on effective intermittent dose used and duration of
adequate response seen or use 2/3 of the initial effective naloxone bolus on an hourly basis
(typically 0.25 to 6.25 mg/hour).
one-half (1/2) of the initial bolus dose should be readministered 15 minutes after initiation of the
continuous infusion to prevent a drop in naloxone levels.
11. Inhalation:
-nebulization: 2 mg; may repeat. Switch to IV or IM administration when possible.
-Intranasal: 4 mg as a single dose in one nostril; may repeat every 2 to 3 minutes in alternating nostrils.
Reversal of respiratory depression with therapeutic opioid doses:
-Initial: 0.02 to 0.2 mg;
-May be given endotracheally as 2 to 2.5 times the initial recommended IV dose (ie, 0.04 to 0.5 mg)
(AHA [Neumar 2010]).
12. For children:
Infants and Children <5 years or ≤20 kg : 0.1 mg/kg/dose (maximum dose: 2 mg); repeat every 2 to
3 minutes if needed.
Children ≥5 years or >20 kg and Adolescents: 2 mg; if no response, repeat every 2 to 3 minutes.
Endotracheal: Infants, Children, and Adolescents: Optimal endotracheal dose unknown; current
expert recommendations are 2 to 3 times the IV dose.
13. DOSING CONSIDERATIONS
Renal Impairment
For Adult and children there are no dosage adjustments.
Hepatic Impairment
For Adult and children there are no dosage adjustments.
16. Hypersensitivity to naloxone or any component of the formulation
CONTRAINDICATIONS
17. WARNINGS/PRECAUTIONS
Acute opioid withdrawal: Administration of naloxone causes the release of catecholamines, which
may precipitate acute withdrawal or unmask pain in those who regularly take opioids.
• Cardiovascular disease: Use with caution in patients with cardiovascular disease or in patients
receiving medications with potential adverse cardiovascular effects; pulmonary edema and
cardiovascular instability, including ventricular fibrillation, have been reported in association with
abrupt reversal when using opioid antagonists.
18. DRUG INTERACTIONS
Methylnaltrexone: May enhance the adverse/toxic effect of Opioid Antagonists. Specifically, the risk
for opioid withdrawal may be increased. Risk X: Avoid combination.
Naldemedine: Opioid Antagonists may enhance the adverse/toxic effect of Naldemedine.
Specifically, the risk for opioid withdrawal may be increased. Risk X: Avoid combination.
Naloxegol: Opioid Antagonists may enhance the adverse/toxic effect of Naloxegol. Specifically, the
risk for opioid withdrawal may be increased. Risk X: Avoid combination.
19. Pregnancy Risk Factor C.
Naloxone crosses the placenta and may precipitate opioid withdrawal in the fetus.
Naloxone is not recommended for use in pregnant women with opioid use disorder except in
situations of life threatening overdose.
Only use if there is a clear indication for use and should not be withheld because of fears of
teratogenicity.
It is not known if naloxone is present in breast milk.
PREGNANCY AND BREAST-FEEDING
23. Background and Objectives: The purpose of this study was to determine the patterns of opioid use
when presenting to an outpatient office for treatment with buprenorphine/naloxone (BUP/NAL) and
its relation to 2012 HB1
Methods: retrospective, multi-site chart review study. total N¼ of 595 from four different medical
locations from January 1, 2009 to July 1, 2016 that provided buprenorphine/naloxone treatment in
Louisville, Kentucky.
Study aims included identifying the most commonly used opioid at the time of treatment before and
after the creation of a state-wide opioid prescribing surveillance system and determine the extent to
which clinical setting, sex, age, and insurance type impacted type of opioid reported during the intake
appointment.
24. A Health Insurance Portability and Account Act waiver, waiver of informed consent, and Institutional
Review Board approval from the University of Louisville and VAMC were obtained.
they obtained an alphabetized list of patients who were currently prescribed BUP/NAL from the
office managers and the two private practices and from the mental health service medical director
of the VAMC.
Were included adult patients (18 years old) who received BUP/NAL at their initial evaluation. Both
male and female patients (including pregnant women) were considered eligible
25. Data from the patient’s initial evaluation was collected regarding self-reported most recently used
opioid(s), sex, age, insurance status, zip code, city, BUP/NAL dose, and date of the initial evaluation.
The opioid(s) that were being used prior to the initial intake were recorded and for the analysis
were subsequently divided into three groups categorized as nonheroin opioid, opioid agonist, or
heroin.
27. The data collected in this study compares the reported use of non-heroin opioid, heroin, and opioid
agonist within the context of state legislation to impact non-heroin opioid prescribing practices.
There has been a notable shift in the opioid epidemic. This retrospective study identified heroin as
the most commonly used drug by patients who sought BUP/ NAL treatment after the enactment of
HB1 and also a significant increase in use of an opioid agonist.
They cant claim a causal relationship due to the nature of our study design. Further research is
necessary to tease out if similar legislations passed in other states resulted in analogous findings
and whether the shift to heroin is a result of the implemented policies or if there are other factors in
play.
CONCLUSION
