Naloxone

VERBATIM (SPC section 4.2, 'Diagnosis and treatment 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.' SECOND, DIFFERENT INDICATION IN THE SAME SPC (verbatim, '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 micrograms/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...' — this smaller titrated regimen is for reversing opioid-induced respiratory depression while preserving analgesia (typically post-operative), NOT for overdose resuscitation; do not confuse the two. ROUTE (verbatim): 'The i.m. administration of Naloxone 400 micrograms/ml should only be used in cases where an i.v. administration is not possible ... 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 ... necessary i.m. dosages are generally higher than i.v. dosages and that dosage has to be adapted to the individual patient.' DURATION AND RE-DOSING (verbatim): 'The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride, varying between 45 minutes and 4 hours ... 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.' INFUSION (verbatim): '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.' No infusion rate is numerically specified in the SPC. ELDERLY (verbatim): '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.' BUPRENORPHINE (section 4.4, verbatim): 'Reversal of buprenorphine-induced respiratory depression may be incomplete. If an incomplete response occurs respiration should be mechanically assisted.' The SPC gives no specific buprenorphine dose. POST-SURGICAL CAUTION (verbatim): '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.'

The dosePerKg figure above is the SPC's paediatric starting dose for SUSPECTED ACUTE OPIOID OVERDOSE. VERBATIM (SPC section 4.2, 'Diagnosis and treatment of suspected acute opioid overdose or intoxication', Children): 'The usual starting dose is 0.01 mg naloxone hydrochloride per kg i.v. If the satisfactory clinical response is not achieved, the dose can be increased in the next injection to 0.1 mg/kg injection. 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.' The escalation figure (a further injection at 0.1 mg per kg) is a per-kg value and is deliberately kept out of maxDose. SECOND, DIFFERENT INDICATION (verbatim, 'Complete or partial reversal of CNS and especially respiratory depression, caused by natural or synthetic opioids', 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.' NEONATES (verbatim, '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).' Concentration 0.4 mg per ml is the source product strength (400 micrograms/ml). WITHDRAWAL RISK: section 4.4 states that too rapid reversal of the opioid effect can cause an acute withdrawal syndrome in patients who have received high doses of opioids or are physically dependent, and 'This also applies to newborn infants of such patients.' Verify any under-18 dose against a children's formulary and local resuscitation policy.