Naloxone

Registered South African indications:

• Opioid-induced respiratory depression

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• High doses of opioids
• Physical opioid dependency
• Infants of mothers with opioid dependence
• Respiratory depression caused by agents other than opioids
• Incomplete reversal (especially buprenorphine-induced respiratory depression)
• Excessive naloxone dosage following surgery
• Rapid opioid reversal
• Cardiovascular disease
• History of taking cardiotoxic agents
• Controlled sodium diet
• May impair the ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Diagnosis and treatment of suspected acute opioid overdose or intoxication

International manufacturer's recommendations

• IV/IM: 0.4-2mg; Repeat every 2-3mins as needed; Max: 10mg

South African Standard Treatment Guidelines' recommendation

• IV/IM: Initial: 0.4mg; Then incremental doses at 2-3min intervals if needed followed by an infusion; Max: 10mg
  Refer to analgesic poisoning: STG, Adult 2019

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If there is no response after a maximum of 10mg of naloxone is administered, the diagnosis of opioid-induced or partial opioid-induced toxicity should be questioned

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Complete or partial reversal of central nervous system and especially respiratory depression caused by natural or synthetic opioids
Postoperative opioid-induced respiratory depression

International manufacturer's recommendations

• IV/IM: Initial: 0.1-0.2mg; Then 0.1mg at 2min intervals if needed until satisfactory response achieved

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An additional injection may be necessary within 1-2hrs, depending on the type of active substance to be antagonised (short-term effect or slow release)

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A continuous IV infusion may be necessary in cases where duration of action of opioids is longer than that of the naloxone IV bolus. Infusion rate is determined according to the individual patient depending on the response of the patient to the IV bolus and the reaction of the patient to the IV infusion

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Can be injected IV or IM or via intravenous infusion

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IM administration only to be used in cases where IV administration is not possible. IM doses are generally higher than IV doses and should be adapted to the individual patient. IM doses also have a longer duration of action than IV administration

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 IV administration is recommended in acute cases as it has the most rapid effect

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Dosage is obtained for each patient in order to obtain optimum respiratory response while maintaining adequate analgesia

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South African Standard Treatment Guidelines' recommendations

• IV: Initial: 0.08mg; Repeat at 2min intervals if needed; Max: 10mg
  Refer to procedural sedation and analgesia: STG, Adult 2019

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Dosage is obtained for each patient in order to obtain optimum respiratory response while maintaining adequate analgesia

Paed. forms avail. in SA and covered in this monograph: inj

Diagnosis and treatment of suspected acute opioid overdose or intoxication

International manufacturer's recommendations

• IV: Initial: 0.01mg/kg; Titrate to 0.1mg/kg if clinical response not achieved

OR

• IM: Initial: 0.01mg/kg; Divided into several doses

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Depending on the individual patient, an IV infusion may also be necessary

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South African Standard Treatment Guidelines' recommendation

• IV: Initial: 0.1mg/kg; Titrate dose according to response if no response after 5mins
  Refer to opioid poisoning: STG, Paed. 2017

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If repeated doses of naloxone are necessary, a continuous IV infusion of naloxone can be instituted

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All patients treated with naloxone should be observed for at least 12 hours for relapse, especially if a long-acting opioid has been ingested

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Complete or partial reversal of central nervous system and especially respiratory depression caused by natural or synthetic opioids
Postoperative opioid-induced respiratory depression

International manufacturer's recommendations

• IV: Initial: 0.01-0.02mg/kg; Repeat every 2-3mins if needed

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Additional doses may be necessary at 1- to 2-hours intervals depending on the response of the patient and the dosage and duration of action of the opiate administered

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South African Standard Treatment Guidelines' recommendation

• IV: 0.01mg/kg, every 2 mins for 4 repeat doses if needed; Max: 0.4mg
  Refer to management of anaesthetic and postanaestheetic complications: STG, Paed. 2017

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All patients need to be kept under direct observation until the effect of the opiates has completely worn off. Further doses of naloxone may be needed as naloxone has a shorter duration of action than most opiates

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Reversal of respiratory and other central nervous system depression in the neonate whose mothers have received opioids

International manufacturer's recommendations

• IV/IM: 0.01mg/kg; Repeat every 2-3mins if needed

South African Standard Treatment Guidelines' recommendation

• Endotracheal (inj)/IV/SC/IM: 0.1mg/kg
  Refer to resuscitation of the newborn: STG, Paed. 2017

Pregnancy

• Caution
• Insufficient clinical data on exposed pregnancies are available
• Animal studies have shown reproductive toxicity. The potential risk for humans is unknown
• The medicinal product should not be used during pregnancy unless clearly necessary. Naloxone hydrochloride can cause withdrawal symptoms in newborn infants

Breastfeeding

• Caution
• It is not known whether naloxone hydrochloride passes into breast milk and it has not been established whether infants who are breastfed are affected by naloxone hydrochloride
• Therefore, breastfeeding should be avoided for 24 hours after treatment

Renal Impairment

• Caution; no information available

Hepatic Impairment

• Caution; no information available

Elderly

• Caution; no dose adjustment recommended
  Use with caution in elderly patients with pre-existing cardiovascular disease or in those receiving potentially cardiotoxic drugs since serious adverse cardiovascular events such as ventricular tachycardia and fibrillation have occurred in postoperative patients following administration of naloxone hydrochloride

Porphyria Information

• Probably not porphyrinogenic (PNP)
  Nausea is a very common side effect that can be potentially porphyrinogenic through reduction in carbohydrate intake and can also be confused with an acute porphyria attack

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Dizziness
• Headache
• Tremor
• Sweating
• Seizures
• Tension

Cardiovascular Disorders

• Tachycardia
• Arrhythmia
  -Ventricular tachycardia
  -Fibrillation
• Bradycardia
• Fibrillation
• Cardiac arrest
• Hypotension
• Hypertension

Respiratory Disorders

• Pulmonary oedema
• Hyperventilation

Gastrointestinal Disorders

• Nausea and vomiting
• Dry mouth
• Diarrhoea

Skin and Subcutaneous Tissue Disorders

• Erythema multiforme
• Irritation of vessel wall (IV administration)
• Local irritation and inflammation (IM administration)

Immune, Blood and Lymphatic System Disorders

• Allergic reactions
  - Urticaria
  - Rhinitis
  - Dyspnoea
  - Quincke's oedema
• Anaphylactic shock

Other

• Postoperative pain
• Return of pain (higher than recommended postoperative use)

• Opioids
• Opioid agonists
• Cocaine
• Methamphetamine
• Tricyclic antidepressants
• Calcium channel blockers
• Beta-blockers
• Digoxin
• Buprenorphine
• Clonidine

Other

• Alcohol

• Respiratory rate
• Heart rate
• Blood pressure
• Temperature
• Level of consciousness
• Arterial blood gases or pulse oximetry

Naloxone hydrochloride, a semisynthetic morphine derivative (N-allyl-nor-oxymorphone), is a specific opioid antagonist that acts competitively at opioid receptors. It reveals very high affinity for the opioid receptor sites and therefore displaces both opioid agonists and partial antagonists. Naloxone hydrochloride does not counteract central depression caused by hypnotics or other non-opioids and does not possess the "agonistic" or morphine-like properties characteristic of other opioid antagonists. In the absence of opioids or agonistic effects of other opioid antagonists, it exhibits essentially no pharmacologic activity. Because naloxone hydrochloride, unlike nalorphine, does not exacerbate the respiratory depression caused by other substances, it can therefore also be used for differential diagnosis.

Injection (per ml) 0.02mg

• Naloxone HCl Neonatal Fresenius (Fresenius Kabi)

Injection (per ml) 0.4mg

• Naloxone HCl- Fresenius (Fresenius Kabi)
• Pharma-Q Naloxone (Pharma Q)