ADMINISTRATION ROUTES:
Intravenous, Intramuscular, Subcutaneous
ICU INDICATIONS:
- Reversal of narcotic respiratory depression and coma
- Itching from neuraxial opioids
PRESENTATION AND ADMINISTRATION:
INTRAVENOUS:
Naloxone 400 micrograms (0.4 mg) in 1 mL vial
Store at room temperature
Compatible with the following intravenous fluids:
- Sodium Chloride 0.9%
- Glucose 5%
Central or peripheral line may be used
Intravenous injection:
Dilute 1 vial (400 micrograms) with 10 mL of compatible fluid, giving concentration of 40 micrograms/mL. Administer over 30 seconds.
Discard any unused portion of the vial immediately
Continuous intravenous infusion:
Dilute 5 vials (2 mg) with 100 mL of compatible intravenous fluid to produce a final concentration of 20 micrograms/mL
Concentrations of up to 40 micrograms/mL may be used if required, e.g. for fluid restricted patients
Administer as a continuous infusion according to the prescription
Discard any unused solution within 24 hours of preparation
INTRAMUSCULAR / SUBCUTANEOUS:
Administer undiluted. Slower onset compared to the intravenous injection by up to 5 minutes. May be used if the intravenous route is unavailable.
DOSAGE:
INTRAVENOUS:
Intravenous injection:
For partial reversal of post-operative respiratory depression or coma:
50 - 200 micrograms (1.5 - 3 micrograms/kg)
Repeat every 2 minutes until desired response
Desired response may be adequate ventilation or alertness without significant pain, depending on indication for use. Depending on opioid dose and clearance, repeat naloxone doses may be required at 1 - 2 hour intervals
For opioid overdose:
400 - 2000 micrograms
Repeat every 2 minutes until desired response
Desired response may be adequate ventilation or alertness
If no response is observed after giving a cumulative dose of 10 mg, consider other causes of respiratory depression
Relatively large doses (up to 3.2 mg) may be required to reverse effects of illicitly manufactured fentanyl and other high-potency opioids. Repeat doses or an infusion may also be required.
Intravenous continuous infusion: If a response to bolus naloxone has been demonstrated, an infusion may be required
Give loading dose equal to 50% of effective reversal dose
Start continuous infusion at 60% of effective reversal dose per hour
Adjust according to response
Note: An effective reversal dose is a dose which maintains satisfactory ventilation for at least 15 minutes i.e. if 600 micrograms total dose required to reverse opioid effect, give 300 micrograms loading dose, then commence infusion at 400 micrograms/h (20 mL/h of 20 micrograms/mL solution) immediately after
INTRAMUSCULAR / SUBCUTANEOUS:
Dose as for intravenous injection. Only use in emergency without intravenous access due to delayed onset.
See the CLINICAL PHARMACOLOGY section below for estimated onset of action per route.
For itching caused by neuraxial opioids:
200 micrograms subcutaneously
Can repeat dose at 30 minutes if no response . Doses > 2 micrograms/kg/hour are likely to reverse the analgesic effect.
DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:
Dose as in normal renal function. Opioids with active metabolites (e.g. morphine, codeine, dihydrocodeine, tramadol) that rely on renal excretion may have an extended half-life in patients with renal impairment
DOSAGE IN HEPATIC IMPAIRMENT:
Dose as in normal liver function
DOSAGE IN PAEDIATRICS:
INTRAVENOUS:
Intravenous injection:
For post-operative respiratory depression or over-sedation:
1 - 20 micrograms/kg (maximum 2 mg/dose)
Repeat every 2 - 3 minutes as required
May also be given subcutaneously, intramuscularly or intratracheally. May require repeat doses every 20 - 60 minutes if the duration of action of opioid is longer than naloxone
For opioid overdose:
100 micrograms/kg
Repeat every 2-3 minutes as required
May also be given subcutaneously, intramuscularly or intratracheally. May require repeat doses every 20 - 60 minutes if the duration of action of opioid is longer than naloxone
Continuous intravenous infusion: If a response to bolus naloxone has been demonstrated, an infusion may be required
Start infusion at 60% of effective reversal dose per hour
Adjust according to response
Note: An effective reversal dose is a dose which maintains satisfactory ventilation for at least 15 minute. i.e. if 600 micrograms total dose required to reverse opioid effect, commence infusion at 400 micrograms/h (20 mL/h of 20 micrograms/mL solution)
CLINICAL PHARMACOLOGY:
- Onset of Action: 2 minutes (intravenous), 2 - 5 minutes (subcutaneous or intramuscular)
- Duration of Action: 30 - 120 minutes
- Elimination: 30 - 90 minutes
Naloxone hydrochloride, is a narcotic antagonist. Naloxone prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. In the presence of physical opioid dependence, naloxone will produce withdrawal symptoms.
CONTRAINDICATIONS:
- Hypersensitivity to naloxone
WARNINGS:
Acute opioid withdrawal
Administration of naloxone may precipitate acute opioid withdrawal or unmask pain in patients on opioids. Symptoms of opioid withdrawal may include pain, tachycardia, hypertension, fever, sweating, abdominal cramps, vomiting, diarrhoea, agitation and irritability. Lower doses are less likely to precipitate severe withdrawal.
Abrupt reversal of narcotic depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure and tremulousness.
Naloxone injection should be administered cautiously to persons including newborns of mothers who are known or suspected to be physically dependent on opioids. In such cases, an abrupt and complete reversal of narcotic effects may precipitate an acute abstinence syndrome.
In post-operative patients, larger than necessary dosages of naloxone may result in significant reversal of analgesia
Incomplete reversal of buprenorphine
Naloxone is not effective against respiratory depression due to non-opioid drugs. Reversal of buprenorphine-induced respiratory depression may be incomplete.
Recurrence of respiratory or CNS depression is possible if the opioid involved is long-acting. Careful observation is recommended and naloxone infusions should be considered for patients who have received long-lasting opioids.
PRECAUTIONS:
General:
In addition to naloxone injection, other resuscitative measures, such as maintenance of an airway, artificial ventilation, cardiac massage and vasopressor agents should be available and employed, when necessary, to counteract acute narcotic poisoning
Cardiovascular disease:
Hypotension, pulmonary oedema and arrhythmias have been reported in association with abrupt withdrawal
Laboratory Tests:
No laboratory tests are required in addition to routine ICU monitoring
Drug/Laboratory Test Interactions:
None known
IMPORTANT DRUG INTERACTIONS IN ICU:
Opioids (fentanyl, morphine, oxycodone): Naloxone reverses opioid effects
ADVERSE REACTIONS:
General:
Return of pain, fever, erythema/reaction at injection site
Cardiovascular:
Flushing, hypertension, hypotension, presyncope, tachycardia, ventricular fibrillation, ventricular tachycardia
Respiratory:
Dry nose, dyspnea, hypoxia, nasal congestion, nasal discomfort (pain), nasal mucosa swelling, respiratory depression, rhinitis, rhinorrhea, sneezing
Neurological:
Agitation, asthenia, body pain, coma, confusion, disorientation, dizziness, encephalopathy, excessive crying (neonates), hallucination, headache, hyperreflexia (neonates), irritability, nervousness, paresthesia, restlessness, seizure (neonates), shivering, tonic-clonic seizure, tremor, withdrawal syndrome, yawning
Gastrointestinal:
Abdominal cramps, abdominal pain, constipation, diarrhea, nausea, oral paresthesia, toothache, vomiting
Hepatic:
Increased serum bilirubin
Dermatological:
Diaphoresis, piloerection, xeroderma
Musculoskeletal:
Muscle spasm, musculoskeletal pain
Metabolic and Endocrine:
Hot flush