Search The Medical Knowledge Base

Drug Details

Naloxone

• Drug Class Description
  Narcotic antagonists.
• Generic Name
  Generic
• Presentation
  Solution for injection Clear and colourless solution pH: 3.1 – 4.5 Osmolality: 270 - 310 mOsMol/kg
• Description
  Each ampoule of 1 ml contains 0.4 mg naloxone hydrochloride (as naloxone hydrochloride dihydrate). Excipient: 1 ml solution for injection contains 3.54 mg of sodium
• Indications
  

  • Complete or partial reversal of CNS and especially respiratory depression, caused by natural or synthetic opioids.

  • Diagnosis of suspected acute opioid overdose or intoxication.

  • Complete or partial reversal of respiratory and other CNS depression in the neonate whose mothers have received opioids.

• Adult Dosage
  

  General

  The medicinal product can be injected intravenously (i.v.) or intramuscularly (i.m.) or can be given via intravenous infusion.

  For incompatibilities and instructions on dilution of the product before administration, see sections 6.2 and 6.6.

  The i.m. administration of Naloxone 400 micrograms/ml should only be used in cases where an i.v. administration is not possible.

  The most rapid effect is obtained by means of i.v. administration, which is why this method of administration is recommended in acute cases.

  When Naloxone 400 micrograms/ml is administered i.m., it is necessary to remember that the onset of action is slower than following i.v. injection; however, i.m. administration has a longer action than i.v. administration. The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride, varying between 45 minutes and 4 hours.

  Furthermore, it has to be considered that necessary i.m. dosages are generally higher than i.v. dosages and that dosage has to be adapted to the individual patient.

  As it is possible that the duration of effect of some opioids (e.g. dextropropoxyphene, dihydrocodeine, methadone) is longer than that of naloxone hydrochloride, the patients must be kept under continuous supervision, and repeated doses must be given if necessary. 

  Complete or partial reversal of CNS and especially respiratory depression, caused by natural or synthetic opioids

  Adults

  Dosage is determined for each patient in order to obtain optimum respiratory response while maintaining adequate analgesia. An i.v. injection of 0.1 to 0.2 mg naloxone hydrochloride (approx. 1.5-3 µg/kg) is usually sufficient. If necessary, additional i.v. injections of 0.1 mg can be administered at 2 minute intervals until satisfactory respiration and consciousness are obtained. An additional injection can again be necessary within 1 to 2 hours, depending on the type of active substance to be antagonised (short-term effect or slow release), the amount administered and time and mode of administration. Naloxone 400 micrograms/ml can alternatively be administered as an i.v. infusion.

  Infusion: The duration of action for some opioids is longer than that of the naloxone hydrochloride i.v. bolus. Therefore, in situations where depression is known to be induced by such substances or there is a reason to suspect this, naloxone hydrochloride should be administered as a continuous infusion. The infusion rate is determined according to the individual patient, depending on the response of the patient to the i.v. bolus and on the reaction of the patient to the i.v. infusion. The use of the continuous intravenous infusion should be carefully considered and respiratory assistance should be applied if necessary.

  Children

  Initially, 0.01-0.02 mg naloxone hydrochloride per kg i.v. at intervals of 2-3 minutes until satisfactory respiration and consciousness are obtained. 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. 

  Diagnosis of suspected acute opioid overdose or intoxication

  Adults

  The initial dose is usually 0.4-2 mg naloxone hydrochloride i.v. If the desired improvement in the respiratory depression is not obtained immediately after i.v. administration, the injections can be repeated at intervals of 2-3 minutes. Naloxone 400 micrograms/ml can also be injected intramuscularly (initial dose usually 0.4-2 mg) if intravenous administration is not possible. If 10 mg naloxone hydrochloride does not produce a significant improvement, this suggests that the depression is wholly or partially caused by other pathological conditions or active substances other than opioids.

  Children

  The usual starting dose is 0.01 mg naloxone hydrochloride per kg i.v. If the satisfactory clinical response is not achieved, an additional 0.1 mg/kg injection can be administered. Depending on the individual patient, an i.v. infusion may also be necessary. If i.v. administration is not possible, Naloxone 400 micrograms/ml can also be injected i.m. (initial dose 0.01 mg/kg), divided into several doses. 

  Reversal of respiratory and other CNS depression in the neonate whose mothers have received opioids

  The usual dosage is 0.01 mg naloxone hydrochloride per kg i.v. If the respiratory function is not reversed to a satisfactory level with this dosage, the injection can be repeated at 2 to 3 minute intervals. If i.v. administration is not possible, Naloxone 400 micrograms/ml can also be injected i.m. (initial dose 0.01 mg/kg).

  Elderly

  In elderly patients with pre-existing cardiovascular disease or in those receiving potentially cardiotoxic drugs, Naloxone 400 micrograms/ml should be used with caution since serious adverse cardiovascular effects such as ventricular tachycardia and fibrillation have occurred in postoperative patients following administration of naloxone hydrochloride.

• Child Dosage
  Neonates, 10 micrograms/kg by intravenous, intramuscular or subcutaneous injection repeated as required; others, 10 micrograms/kg by intravenous, intramuscular or subcutaneous injection repeated as required or by intravenous infusion; see data sheet.  sheet.
• Contra Indications
  

  Naloxone 400 micrograms/ml is contraindicated in patients with hypersensitivity to naloxone hydrochloride or to any of the excipients of this medicinal product.

• Special Precautions
  

  Naloxone 400 micrograms/ml must be given with caution to patients who have received high doses of opioids or are physically dependent on opioids. Too rapid reversal of the opioid effect can cause an acute withdrawal syndrome in such patients. Hypertension, cardiac arrhythmias, pulmonary oedema and cardiac arrest have been described. This also applies to newborn infants of such patients.

  Patients who respond satisfactorily to naloxone hydrochloride must be closely monitored. The effect of opioids can be longer than the effect of naloxone hydrochloride and new injections may be necessary.

  Naloxone hydrochloride is not effective in central depression caused by agents other than opioids. Reversal of buprenorphine-induced respiratory depression may be incomplete. If an incomplete response occurs respiration should be mechanically assisted.

  Following the use of opioids during surgery, excessive dosage of naloxone hydrochloride should be avoided, because it may cause excitement, increase in blood pressure and clinically important reversal of analgesia. A reversal of opioid effects achieved too rapidly may induce nausea, vomiting, sweating or tachycardia.

  Naloxone hydrochloride has been reported to induce hypotension, hypertension, ventricular tachycardia, fibrillation and pulmonary oedema. These adverse effects have been observed postoperatively most often in patients who have cardiovascular diseases or who have used medicines with similar cardiovascular adverse effects. Although no direct causative relations have been shown, caution should be used in administering Naloxone 400 micrograms/ml to patients with heart diseases or to patients who are taking relatively cardiotoxic drugs causing ventricular tachycardia, fibrillation and cardiac arrest (e.g. cocaine, methamphetamine, cyclic antidepressants, calcium channel blockers, beta-blockers, digoxin).

  This medicinal product contains 3.8 mmol (88.5 mg) sodium per maximum daily dose of 10 mg naloxone hydrochloride. This should be taken into consideration by patients on a controlled sodium diet.

• Interactions
  

  The effect of naloxone hydrochloride is due to the interaction with opioids and opioid agonists. When administered to subjects dependent on opioids, in some subjects the administration of naloxone hydrochloride can cause pronounced withdrawal symptoms. Hypertension, cardiac arrhythmias, pulmonary oedema and cardiac arrest have been described.

  With a standard naloxone hydrochloride dose there is no interaction with barbiturates and tranquillizers.

  Data on interaction with alcohol are not unanimous. In patients with multi-intoxication as a result of opioids and sedatives or alcohol, depending on the cause of the intoxication, one may possibly observe a less rapid result after administration of naloxone hydrochloride.

  When administering naloxone hydrochloride to patients who have received buprenorphine as an analgesic complete analgesia may be restored. It is thought that this effect is a result of the arch-shaped dose-response curve of buprenorphine with decreasing analgesia in the event of high doses. However, reversal of respiratory depression caused by buprenorphine is limited.

  Severe hypertension has been reported on administration of naloxone hydrochloride in cases of coma due to a clonidine overdose.

• Adverse Drug Reactions
  

  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.

  Skin and subcutaneous tissue disorders

  Very rare: Erythema multiforme

  One case of erythema multiforme cleared promptly after naloxone hydrochloride was discontinued.

  General disorders and administration site conditions

  Common: Postoperative pain

  Uncommon: Hyperventilation, irritation of vessel wall (after i.v. administration); local irritation and inflammation (after i.m. administration)

  Higher than recommended dosage in postoperative use can lead to the return of pain.

  A fast reversal of opioid effect can induce hyperventilation.