- naloxone hydrochloride dihydrate
POM: Prescription only medicine
This information is intended for use by health professionals
GeneralThe 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
AdultsDosage 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.
ChildrenInitially, 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
AdultsThe 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.
ChildrenThe 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 opioidsThe 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).
ElderlyIn 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.
PregnancyFor Naloxone hydrochloride insufficient clinical data on exposed pregnancies are available. Animal studies have shown reproductive toxicity (see section 5.3). 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 new-born infants (see section 4.4).
LactationIt is not known whether naloxone hydrochloride passes into breast milk and it has not been established whether infants who are breast-fed are affected by naloxone hydrochloride. Therefore, breast-feeding should be avoided for 24 hours after treatment.
|Immune system disorders|
|Very rare:||Allergic reactions (urticaria, rhinitis, dyspnoea, Quincke's oedema), anaphylactic shock|
|Nervous system disorders|
|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.|
|Very rare:||Fibrillation, cardiac arrest|
|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.|
|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|
|Uncommon:||Hyperventilation, irritation of vessel wall (after i.v. administration); local irritation and inflammation (after i.m. administration)|
AbsorptionNaloxone hydrochloride is rapidly absorbed from the gastrointestinal tract but it is subject to considerable first-pass metabolism and is rapidly inactivated following oral administration. Although the drug is effective orally, doses much larger than those required for parenteral administration are required for complete opioid antagonism. Therefore, naloxone hydrochloride is administered parenterally.
DistributionFollowing parenteral administration, naloxone hydrochloride is rapidly distributed into body tissues and fluids, especially into the brain, because the drug is highly lipophilic. In adult humans, the distribution volume at steady-state is reported to be about 2 l/kg. Protein binding is within the range of 32 to 45 %.Naloxone hydrochloride readily crosses the placenta; however, it is not known whether naloxone hydrochloride is distributed into breast milk.
MetabolismNaloxone hydrochloride is rapidly metabolised in the liver, mainly by conjugation with glucuronic acid, and excreted in urine.
EliminationNaloxone hydrochloride has a short plasma half-life of approximately 1-1.5 hours after parenteral administration. The plasma half-life for neonates is approximately 3 hours. The total body clearance amounts to 22 ml/min/kg.
Shelf-life after first openingAfter first opening the medicinal product should be used immediately.
Shelf-life after dilutionChemical and physical in-use stability has been demonstrated for 24 hours below 25°C.From the microbiological point of view, the dilutions should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2 to 8 °C, unless dilution has taken place in controlled and validated aseptic conditions.