NALOXONE HYDROCHLORIDE

9%) or 5% dextrose in water or saline: the addition of 2mg (2ml of 1mg/1ml concentration) of Naloxone in 500ml of either solution provides a concentration of 4 micrograms/ml. Mixtures should be used within 12 hours. After 12 hours, the remaining unused solution must be discarded.

The rate of administration should be titrated in accordance with the patient’s response to both Naloxone infusion and to any previous bolus doses administered. Parenteral drug products should be inspected visually for particulate matter and discolouration prior to administration whenever solution and container permit.

Adults:

Opioid overdosage (known or suspected) An initial dose of 400 to 2000 micrograms of Naloxone may be administered intravenously. If the desired degree of counteraction and improvement in respiratory function is not obtained it may be repeated at 2 to 3 minute intervals.

If no response is observed after 10mg of Naloxone have been administered the diagnosis of opioid-induced or partial opioid induced toxicity should be questioned. Intramuscular or subcutaneous administration may be necessary if dosing by the intravenous route is not feasible.

B. g. dextropropoxyphene (present in commonly prescribed analgesics which in over-dosage have been associated with suicide), dihydrocodeine and methadone. In situations where one of these opioids is known or suspected it is recommended that an infusion of Naloxone be used to produce sustained antagonism to the opioid without repeated injection.

Post Operative Use When Naloxone is used postoperatively, the dose should be titrated for each patient in order to obtain optimum respiratory response while maintaining adequate analgesia. 5-3 micrograms/kg body weight) are usually sufficient, but a full two minutes should be allowed between each 100 micrograms increment of Naloxone administered.

e. long or short-acting) of drug used. Alternatively Naloxone may be administered as an intravenous infusion (see above). v. If this dose does not result in the desired degree of clinical improvement, a subsequent dose of 100 micrograms/kg of bodyweight may be administered.

Naloxone may be required by infusion as described above. v. m. c. in divided doses. Neonatal Use An adequate airway should be established in the apnoeic infant before Naloxone is administered. c.. If the desired degree of counteraction and improvement in respiratory function is not obtained it may be repeated at 2-3 minute intervals.

The following frequency terminology is used:

Very common: ≥ 1/10; Common: ≥ 1/100, < 1/10; Uncommon: ≥ 1/1,000, < 1/100; Rare: ≥ 1/10,000, < 1/1,000; Very rare: < 1/10,000; Not known (cannot be estimated from the available data) Immune system disorders Very rare: Allergic reactions (urticaria, rhinitis, dyspnoea, Quincke's oedema), anaphylactic shock Nervous system disorders Common: Dizziness, headache Uncommon: Tremor, sweating Rare: Seizures, tension Seizures have occurred rarely following administration of naloxone hydrochloride; however, a causal relationship to the drug has not been established.

Higher than recommended dosage in postoperative use can lead to tension.

Cardiac disorders Common:

Tachycardia Uncommon: Arrhythmia, bradycardia Very rare: Fibrillation, cardiac arrest Vascular disorders Common: Hypotension, hypertension Hypotension, hypertension and cardiac arrhythmia (including ventricular tachycardia and fibrillation) have also occurred with the postoperative use of naloxone hydrochloride.

Adverse cardiovascular effects have occurred most frequently in postoperative patients with a pre-existing cardiovascular disease or in those receiving other drugs that produce similar adverse cardiovascular effects.

Respiratory, thoracic and mediastinal disorders Very rare:

Pulmonary oedema Pulmonary oedema has also occurred with the postoperative use of naloxone hydrochloride.

Gastrointestinal disorders Very common:

Nausea Common: Vomiting Uncommon: Diarrhoea, dry mouth Nausea and vomiting have been reported in postoperative patients who have received doses higher than recommended. However, a causal relationship has not been established, and the symptoms may be signs of too rapid antagonisation of the opioid effect.

It should be administered cautiously to patients who have received large doses of opioids or to those physically dependent on opioids since too rapid reversal of opioid effects by Naloxone may precipitate an acute withdrawal syndrome in such patients.

The same caution is needed when giving Naloxone to neonates delivered of such patients. Hypertension, cardiac arrhythmias, pulmonary oedema and cardiac arrest have been described. The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include but are not limited to the following: body aches, diarrhoea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea, vomiting, nervousness, restlessness, irritability, shivering, trembling, abdominal cramps, weakness and increased blood pressure.

In the neonate, opioid withdrawal may also include: convulsions, excessive crying and hyperactive reflexes. Patients who have responded satisfactorily to Naloxone should be kept under observation. Repeated doses of Naloxone may be necessary since the duration of action of some opioids may exceed that of Naloxone.

Naloxone is not effective against respiratory depression caused by non-opioid drugs. Reversal of buprenorphine-induced respiratory depression may be incomplete. If an incomplete response occurs, respiration should be mechanically assisted.

Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest which may result in death.

Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest have been reported in postoperative patients. Death, coma and encephalopathy have been reported as sequelae of these events.

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